Neuronal migration is critical for mammalian brain development. In many migrating neurons, the nucleus translocates from the trailing to the leading edge of the cell in a manner dependent on the actin and microtubule cytoskeletons, but how these cytoskeletons interact and their relative contribution to the forces that move the nucleus has remained unclear. This week we feature a paper published in the latest issue of Development that uses live imaging to understand this process, revealing some fascinating cellular behaviours. We caught up with first author You Wu and his supervisor  Mineko Kengaku, Professor at the Institute for Integrated Cell-Material Sciences at Kyoto University, to find out more about the story.

Mineko, can you give us your scientific biography and the questions your lab is trying to answer?

MK We study how neurons are built up into the beautiful architecture of the brain cortex. A major effort of my lab has been devoted to live-imaging of growing neurons for a mechanistic understanding of brain formation, using the clear and simple cerebellar cortex as a model. We especially focus on the mechanisms and dynamics of cytoskeletal organization during migration of granule cells and dendrite arborization of Purkinje neurons, the two major events during the formation of the three-layered cortex of the cerebellum. I did my PhD study on the molecular mechanism of the primary axis formation in the Xenopus CNS, under supervision of Dr Harumasa Okamoto at the University of Tokyo. I wanted to further study the molecular signals regulating morphogenesis, and joined the laboratory of Cliff Tabin at Harvard Medical School as a post-doc. His lab had just discovered Sonic hedgehog as a bona fide morphogen in the chick embryo. I was extremely lucky to be present in the lab at moments when long-standing questions were clarified, such as the mechanisms of left-right asymmetry, bone formation, fore- and hind limb differentiation, etc. As a consequence of this rapid progress, many fundamental questions in morphogenetic signals had been clarified by the time I started my own lab at the RIKEN Brain Science Institute.  The major interests in developmental biology then shifted toward stem cells and disease mechanisms. But I was still fascinated with animal morphology, and therefore decided to look into the beautiful shapes of neurons in the well-organized cortex of the brain.

And You, how did you come to be involved with this project?

YW I was attracted by the beautiful morphology of neurons and the structure of the cortex, and joined the Kengaku Lab as a Master’s student. I first worked on hippocampal neurons to seek how they achieve their unique dendritic shape by live-imaging. The dynamics of development really excited me. Around the time I completed my M.S. degree, I saw a movie of nuclear rotation in a migrating neuron, and was simply interested in the phenomenon.

What was known about the role of the cytoskeleton in CGC nuclear migration before your work?

MK & YW Unlike mesenchymal cell migration, neurons typically form a long leading process and move the nucleus into the leading process in a saltatory manner independently of the constant leading process extension. Since the discovery of an evolutionary conserved cytoplasmic dynein complex protein LIS1 as a responsible gene for smooth brain syndrome (type 1 lissencephaly), accumulating evidence has supported the model that the nucleus is pulled forward by dynein motor activity along the microtubules extended from the leading process. Subsequent studies have also implicated the contractile force of actomyosin in nuclear movement, although competing hypotheses for the site of actomyosin force generation have been proposed using different neuron models.

CGC migration has provided an in vitro model for cell biology study of neuronal migration ever since the first time-lapse observations in 1980s. Recent studies from the groups of Xiao-bing Yuan and David Solecki have provided strong evidence that actomyosin localized in the proximal leading process exerts the driving force for nuclear migration in CGCs. However, the precise interplay and relative contribution of actomyosin and microtubules during nuclear migration have remained to be elucidated.

Can you give us the key results of the paper in a paragraph?

MK & YW For better understanding of the complicated interplay between microtubule- and actin-dependent mechanisms driving nuclear migration in CGCs, we performed a high spatiotemporal resolution imaging using spinning-disk confocal microscopy. We found that the nucleus displayed unexpectedly dynamic motion during migration, including fast rotation in the soma. By quantitative 3D image analysis combined with molecular and pharmacological manipulations, we demonstrated that the nuclear rotation is driven by the same strain energy inducing nuclear translocation. Furthermore, among the two major cytoskeletal forces driving nuclear migration, rotation is solely dependent on microtubule systems but not actomyosin, while nuclear translocation requires both actomyosin and microtubules. We thus used nuclear rotation as a readout of microtubule-dependent tensile stress during nuclear migration, which led to the second major finding that both dynein and kinesin-1 are involved in the force transmission. Our results suggest that microtubules and associated bidirectional motors exert force to small points on the nuclear envelope via interaction with nesprins, and steer rotation or translocation depending on the position of the force points.

I have to say that the videos in your paper are remarkably beautiful! Can you tell me what it was like to first see nuclear rotation in migrating CGCs?

MK Our co-author Hiroki Umeshima is highly skilled in live imaging, and he set up most of the imaging systems used in the present study. His first movie of nuclear rotation caught my eye, but I did not begin the present study for more than a year, as I was unsure if the rotation is a biologically significant event or an idling motion caused by excessive force to the nucleus in culture. But, the more movies I watched, the more confident I became that the rotation was driven by active forces on small points of the nucleus during nuclear migration.  Around that time, You had developed his skill in image analysis, so I asked him if he was interested in analyzing this mysterious phenomenon, and he said ‘Yes’.

YW It was really interesting. I never imagined the nucleus would rotate so fast and frequently during migration. The movies also showed the dynamic deformation of the nucleus. I reckoned these motions could be indicating force transmission, and started to find a way to analyze the dynamics.

How do you think the opposing microtubule motors dynein and kinesin work together to drive unidirectional nuclear motion?

MK & YW We observed frequent switches of rotation direction both in vivo and in vitro (Movie 4 and 5), indicating that the nuclear surface readily moves in both anterograde and retrograde directions by dynamic interplay of the bidirectional motors on bipolar microtubules. Given that the polarity of perinuclear microtubules is mixed but strongly biased, dynein probably acts as the predominant motor and moves the nucleus along the retrograde microtubules (with minus-end toward the leading process) as previously indicated, while kinesin drives back-step movement or rotation. Involvement of bidirectional motors in nuclear migration along uniformly oriented microtubules has been found in long hypodermal precursor cells in nematode embryos (Bone et al., Development 2016; Fridolfsson and Starr, Dev. Biol. 2010). Both hypodermal cells and CGCs are elongated and move nuclei through narrow interstitial and tissue spaces, where dynamic bi-directional movement by opposing motors might adjust the precise positioning of the nucleus and help it squeeze through constrictions.

When doing the research, did you have any particular result or eureka moment that has stuck with you?

I was excited to observe the dynamics of the nucleus in the organotypic slice culture. Until then, I was focused on the in vitro culture system, where the rotation and deformation occurs sporadically. I found the nucleus in 3D tissue much more dynamic, and there was almost no moment when the nucleus stayed still. It was interesting to see that forces seemed to be always applied to the nucleus, even if it was not translocating

And what about the flipside: any moments of frustration or despair?

While it was an exciting moment to see the nuclear motion in tissue, it was very challenging to analyse it quantitatively. It would be interesting and informative to characterize its properties in tissue precisely, but it was difficult to acquire enough resolution in live-imaging.

What next for you, You?

It is always fun for me to observe dynamic things. I am still interested in neural development and also in brain function, which is achieved by such well-organized structure, and am thinking about doing postdoc in related fields.

Where will this work take the Kengaku lab?

We want to further elucidate the actual crosstalk of microtubule motors and nuclear envelope during nuclear motion. New imaging techniques with higher spatiotemporal resolution might be required to pursue the next problem. Also, the dynamic deformation and rotation shown in the present study suggest that the nucleus is very soft and flexible in newborn neurons. We are interested in how the mechanical properties of the nucleus is determined, and if they contribute to neuronal migration.

Finally, let’s move outside the lab – what do you like to do in your spare time?

MK I must confess that I do not have so much spare time for special activities after research and family. I am a food fan and enjoy cooking every day. I sometimes eat-out with my family and friends on weekends. Luckily Kyoto is a great place to explore nice restaurants of various styles, from traditional Japanese Kaiseki to casual French bistro.

YW I like to sing songs, sometimes in a bit loud voice if nobody is by.

Nesprins and opposing microtubule motors generate a point force that drives directional nuclear motion in migrating neurons. You Kure Wu, Hiroki Umeshima, Junko Kurisu, Mineko Kengaku. Development 2018 145: dev158782

This is #37 in our interview series. Browse the archive here. 

(2 votes)

Loading...

Daniel Pederick & Paul Thomas

Comment on our paper: Pederick, et al. 2018. Abnormal Cell Sorting Underlies the Unique X-Linked Inheritance of PCDH19 Epilepsy. Neuron 97 (1).

Here we discuss the curious case of female-restricted epilepsy, an unusual disorder caused by mutations in the Protocadherin 19 (PCDH19) gene. How changes in this cell adhesion gene cause seizures and intellectual disability in girls (but not boys) has been a mystery since this condition was first described over 20 years ago. By pursuing several lines of enquiry including in vitro cell sorting assays, CRISPR/Cas9 mouse models and patient MRIs, we have finally “cracked the case”, although intriguing questions remain about the neuronal pathology that underpins this unique condition.

PCDH19-GCE-no other disorder is quite like it

The most striking characteristic of PCDH19-GCE is its unique X-linked inheritance pattern which was first described by Ryan et al in 1997. Typically, X-linked disease-causing mutations affect males as they do not have a second wild type (WT) copy of the gene to compensate. As the name suggests, Protocadherin 19 Girls Clustering Epilepsy (PCDH19-GCE) is caused by mutation in the X-linked gene PCDH19 but this disorder does not follow the “typical” X-linked recessive disease inheritance pattern. Instead, heterozygous females (who have one WT copy and one mutated copy of the PCDH19) are affected while hemizygous males are not.  A mysterious condition indeed!

It was not until 2008 that PCDH19 mutations were identified as causing the disease, and multiple hypotheses were put forward to explain its unusual inheritance pattern. It was initially proposed that PCDH19 mutations may be dominant negative, but the identification of whole gene deletions and examples of nonsense mediated decay provided strong evidence opposing this hypothesis (Dibbens et al., 2008). It was also suggested that males may be able to compensate for the loss of PCDH19 through the Y-linked PCDH11Y gene. However, this has also been ruled out due to the discovery of several mosaic males with early somatic mutations in PCDH19 that phenocopy affected girls (Depienne et al., 2009; Terracciano et al., 2016). The third and final hypothesis was based on two key facts. The first is that PCDH19 is located on the X-chromosome and is subject to X-inactivation. This mechanism ensures that females randomly “silence” one copy of the X chromosome in every cell to match the expression levels in males (who are XY). Thus, females with PCDH19 mutations have a mixture of WT and mutant neurons. The second was PCDH19’s known role as a homotypic cell adhesion molecule. Together these pieces of information led Dibbens et al , 2008 and Depienne et al 2009 to suggest that mosaic expression of PCDH19 in female brains leads to abnormal neuronal connections between PCDH19 WT and PCDH19 mutant cells affecting neural network formation and ultimately giving rise to seizures and intellectual disability. However, it was unclear how mosaicism could lead to PCDH19-GCE at the molecular, cellular and network level. Furthermore, this model did not explain why the complete absence of PCDH19 (in males) does not cause epilepsy.

The smoking gun: cell sorting assays provide evidence for a PCDH adhesion code

We attempted to unravel this mystery by combining complementary in vitro and in vivo experimental approaches. A valuable clue came from recent papers showing that clustered PCDHs (which are structurally similar to the non-clustered PCDH family to which PCDH19 belongs) act in combination to form complexes at the cell surface with highly specific homotypic binding affinities (Thu et al., 2014). This peaked our interest as it was unclear from the “cellular interference model” how the loss of a single cell adhesion molecule could disrupt normal interactions given that neurons typically express many PCDH family members. Using a co-immunoprecipitation and cell aggregation assays we demonstrated that PCDH19 can form promiscuous cis and highly specific trans interactions both of which are required to generate specific combinatorial binding affinities. We then mixed together two populations of cells expressing different combinations of PCDHs and observed segregation between the two populations when they differed by just a single PCDH (Figure 1). This confirmed that the “PCDH adhesion code” was acutely sensitive to the absence of PCDH19.

The next step was to assess how disruption of PCDH19-dependent adhesion would impact the developing brain, where a complex array of cell adhesion molecules and binding partners are expressed. To investigate this, we turned to our previously characterised Pcdh19 Knockout (KO) mouse model (Pederick et al., 2016).  Like humans, Pcdh19 is located on the X chromosome in mice and therefore heterozygous mice have mosaic expression of Pcdh19 due to X-inactivation. Interestingly, electrocorticogram analysis revealed significantly elevated activity in heterozygous mice when compared to WT controls. Importantly, this phenotype was not present in mice completely lacking Pcdh19, which matched the unique X-linked inheritance of PCDH19 epilepsy.

CRISPR/Cas9 joins the investigation

While the electrical phenotype of the mouse was consistent with humans, we couldn’t investigate the cellular impact of mosaic PCDH19 expression in the brain because we were lacking a specific PCDH19 antibody with which to identify PCDH19+ cells. We therefore turned to the CRISPR/Cas9 genome editing system and generated a mouse with an epitope-tagged (HA-FLAG) version of PCDH19, allowing us to identify PCDH19 WT cells with commercially available antibodies. To detect “PCDH19-expressing” Pcdh19 null cells we used the previously mentioned PCDH19 KO mouse which has a LacZ reporter. Now we were set to answer the key question- how does mosaic expression of Pcdh19 in heterozygous female brains affect the behaviour of the WT PCDH19 and null PCDH19 cell populations?

Simultaneous labelling of WT PCDH19 and null PCDH19 cells in PCDH19 heterozygous mice revealed a striking pattern of alternating PCDH19 +ve and PCDH19 -ve regions (Figure 2). This pattern was particularly obvious in the developing cortex where it resembled “tiger stripes”. Before getting too excited, we needed to address the possibility that the apparent segregation simply arose from X-inactivation and subsequent clonal expansion of PCDH19 +ve and PCDH19 -ve cells. We therefore generated “WT” mice with one tagged copy of PCDH19 and one (untagged) WT PCDH19 allele. This critical control was only possible because we had generated the tagged allele (i.e. even if we had a PCDH19 Ab we could not have done this experiment). Critically, there was no sign of the “tiger stripes” in this control- instead we detected small patches of tagged and untagged PCDH19 cells along the ventricle with subtle variations in the cortical plate (Figure 2). So, evidence for active cell segregation in heterozygous females was beginning to stack up.  Interestingly, the abnormal segregation pattern of WT PCDH19 and null PCDH19 cells was different in each mouse, presumably caused by the random nature of X-inactivation. Since the symptoms of PCDH19 epilepsy are highly variable (even in identical twins (Higurashi et al., 2012)) it is possible that different segregation patterns contribute to the severity of the disorder. Although not performed in this study it would be interesting to correlate the X-inactivation patterns seen in individual mice with their ECoG recordings to identify any patterns that lead to higher electrical brain activity.

In our opinion the most interesting feature of PCDH19 epilepsy is not that mosaicism leads to disease but that individuals who completely lack PCDH19 do not have the disease. As mentioned above, homozygous null mice did not display increased electrical brain activity. We hypothesised that this phenotypic “rescue” was due to the uniform loss of Pchd19 and the consequent restoration of normal cell sorting during cortical development. To test this, we developed a strategy to rapidly assess in vivo cell sorting in Pcdh19 null embryos. We deleted the functional PCDH19^TAG allele in heterozygous (PCDH19^TAG/PCDH19^LACZ) zygotes using CRISPR/Cas9, transferred the embryos to pseudopregnant females for further development, and then used X-Gal staining to track the location of the PCDH19 null cells. While negative (i.e. heterozygous) controls showed the expected segregation phenotype, no significant segregation occurred after deletion of the (WT) PCDH19^TAG allele. These findings provided further evidence that abnormal cell sorting is caused by the differential adhesion affinities between WT PCDH19 and null PCDH19 cells. Furthermore, the absence of abnormal cell sorting in animals completely lacking PCDH19 provides a clear cellular phenotype that explains the unique inheritance pattern of PCDH19 epilepsy.

Finally, we postulated that abnormal cell sorting in humans could lead to brain malformations due to the prolonged expansion and increased cortical folding compared to mice. Abnormal cortical sulcation was observed in four girls with causative PCDH19 mutations. We identified variably positioned cortical defects that included bottom of the sulcus dysplasias, abnormal cortical folding, cortical thickening and blurring of the grey/white junction. It is not known how abnormal cell sorting may generate these cortical malformations, however, insight into the cellular mechanism could be gained by the generating a PCDH19 mutant ferret with CRISPR/Cas9 genome editing, a model organism that has extensive cortical folding.

For the future…

These findings provide some long-awaited answers to the mysterious inheritance of PCDH19 epilepsy. However, despite these insights, there is still much to discover about how mosaic expression of PCDH19 leads to epilepsy, intellectual disability and autism. It is possible that in addition to cell sorting, other processes such as neuronal wiring, synapse formation, maintenance and function are disrupted by differential adhesion affinities caused by mosaic expression of PCDH19. Perturbation of these fundamental neuronal processes is implicated in many neurodevelopmental disorders and it seems possible that they may also be altered in PCDH19 epilepsy. Much sleuthing lies ahead!

References

Depienne, C., Bouteiller, D., Keren, B., Cheuret, E., Poirier, K., Trouillard, O., Benyahia, B., Quelin, C., Carpentier, W., Julia, S., et al. (2009). Sporadic Infantile Epileptic Encephalopathy Caused by Mutations in PCDH19 Resembles Dravet Syndrome but Mainly Affects Females. PLoS Genet 5, e1000381.

Dibbens, L.M., Tarpey, P.S., Hynes, K., Bayly, M.A., Scheffer, I.E., Smith, R., Bomar, J., Sutton, E., Vandeleur, L., Shoubridge, C., et al. (2008). X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment. Nat. Genet. 40, 776–781.

Higurashi, N., Shi, X., Yasumoto, S., Oguni, H., Sakauchi, M., Itomi, K., Miyamoto, A., Shiraishi, H., Kato, T., Makita, Y., et al. (2012). PCDH19 mutation in Japanese females with epilepsy. Epilepsy Res. 99, 28–37.

Pederick, D.T., Homan, C.C., Jaehne, E.J., Piltz, S.G., Haines, B.P., Baune, B.T., Jolly, L.A., Hughes, J.N., Gecz, J., and Thomas, P.Q. (2016). Pcdh19 Loss-of-Function Increases Neuronal Migration In Vitro but is Dispensable for Brain Development in Mice. Scientific Reports 6, srep26765.

Ryan SG, Chance PF, Zou CH, Spinner NB, Golden JA, Smietana S. (1997) Epilepsy and mental retardation limited to females: an X-linked dominant disorder with male sparing. Nat Genet. 17, 92-5

Terracciano, A., Trivisano, M., Cusmai, R., De Palma, L., Fusco, L., Compagnucci, C., Bertini, E., Vigevano, F., and Specchio, N. (2016). PCDH19-related epilepsy in two mosaic male patients. Epilepsia.

Thu, C.A., Chen, W.V., Rubinstein, R., Chevee, M., Wolcott, H.N., Felsovalyi, K.O., Tapia, J.C., Shapiro, L., Honig, B., and Maniatis, T. (2014). Single-cell identity generated by combinatorial homophilic interactions between α, β, and γ protocadherins. Cell 158, 1045–1059.

(3 votes)

Loading...

Applications are sought from established as well as career development researchers with interests in nervous system and/or human development, including stem cells and organoid approaches. We are also seeking cell biologists with interests in signalling, trafficking and cell adhesion.

Applicants will be expected to be competitive for personal fellowships and/or programme level grant support and have a strong publication record. For career development researchers the start-up package typically includes financial support for relocation and

essential equipment and a defined transition to tenure after 5-6 years. New researchers are supported by a structured mentoring programme. The University of Dundee operates policies enabling flexible working to ensure a good work life balance.

The Division of Cell & Developmental Biology consists of 8 research groups studying the regulation of differentiation in developing organisms, stem cells and adult tissues and how this is altered in disease states. Our work combines classical embryology, cell biological and genetic approaches as well as mathematical modelling to understand gene function and regulation in differentiating tissues. A particular shared interest is in epithelial cell biology, and this has led to our cooperative effort to maintain and develop state of the art imaging technologies. The Division also hosts the Dundee Human Pluripotent Cell Facility, which provides quality controlled human pluripotent cells and training in their use.

How to apply: please provide CV, details of 3 academic referees and a brief summary of future research plans. For informal enquiries please contact

Prof. Kate Storey k.g.storey@dundee.ac.uk

or Prof. Inke Nathke i.s.nathke@dundee.ac.uk

Full job description: https://www.dundee.ac.uk/jobs

Reference no: SLSC0338

Closing date: April 30^th 2018

(No Ratings Yet)

Loading...

The Institut de Génomique Fonctionnelle de Lyon (IGFL) has an opening for a new independent group leader. The IGFL has a unique scientific profile and fosters an outstanding international environment. Teams address basic research questions at the interfaces of evolution, physiology and development using functional genomics, bioinformatics, genetics and comparative approaches. The IGFL has a strong focus on integrative, organism-level research using a diversity of model and non-model organisms.

More information at: https://www.nature.com/naturejobs/science/jobs/636517-research-group-leader-opening

The deadline for applications is April 2nd.

(No Ratings Yet)

Loading...

You can find our recently published eLife paper here.

At the Euro-Evo-Devo meeting in Lisbao I saw a talk by Sylvie Rétaux and became hooked by a blind and unpigmented cavefish: the evo-devo model Astyanax mexicanus. I then had the chance to join Sylvie’s group in Gif-sur-Yvette (France) in 2013, for a post-doc. Four years later we come out with this paper of which I’m extremely happy, not least because this study owes a great deal to teamwork and wouldn’t have been possible without a fantastic collaborative spirit between enthusiast and passionate team members. Because the “author contribution” section didn’t quite capture my feeling about the human adventure behind our paper, I’d like to take this blog post as a platform to properly acknowledge each of my friends and bring to you our scientific/team-story.

Astyanax mexicanus, evo-devo top model

Astyanax mexicanus is a teleost fish that inhabits South American rivers. As well as the river dwelling fish, several Astyanax populations can be found deep in the caves of the Sierra del Abra in Mexico. Cave colonization has occurred several times independently and these cave populations have experienced convergent evolution of several traits, including loss of eyes and pigmentation. Cave fish also behave differently than their surface siblings, probably in response to selective forces driving adaptation to life in complete and permanent darkness. For instance, they have a better sense of smell and more appetite, they swim more and sleep less, almost constantly exploring their environment in the quest for food or sexual partner. Astyanax is a great model to link developmental evolution with adaptation to a new environment. By comparing the anterior brain of surface and cave fish, and by doing so in young embryos, Sylvie’s team have been highlighting how development of the central nervous system has shaped cavefish evolution.

Our recently published work makes a new contribution to the story of Astyanax brain evo-devo. And for the first time we were able to elucidate some links between early embryonic development and fish behavior. To reach this goal, it tooks 4 years, 3 co-first authors (me-Alexandre Alié, Jorge Torres-Paz and Lucie Devos), the contribution of two brilliant students (Lise Prunier and Fanny Boulet), the unwavering support of our lab manager (Maryline Blin) and the expertise of our specialist in behavioral studies (Yannick Elipot).

From early development…

The story began before I joined the group, with the work of Lise. At that time she was a Master’s degree student and had performed very numerous and beautiful in situ hybridization showing more NPY neurons in cavefish brain versus more Pomcb neurons in surface fish brain. When Lise had to leave the lab at the end of her internship, Sylvie offered me to dig deeper into this story. Together with Maryline, I started to characterize the expression of 9 neuropeptides, at 4 embryonic stages in the 2 morphotypes (cave versus surface)… 72 different conditions in total, reproduced several times to get statistics. This could have been frustrating at some point, but few weeks after I started Lucie joined our lab for her master internship. Lucie galvanized us with her contagious enthusiasm! Our hours spent at the microscope to count/recount neurons or to debate the anatomical interpretations of our results became so much more fun by our combined efforts.

We next embarked on a series of double fluorescent ish to establish a co-expression map between Lhx genes and neuropeptides. Again, help was at hand from a skillful student, Fanny, who did a fantastic job with these double FISH (no pun intended), under the ever-watchful eye of Maryline. We have the chance to possess a fancy confocal microscope in the lab, and we were so excited to get into the very intimacy of Astyanax brain. The expression domains and dynamics of Lhx7 and Lhx9 strongly suggested a role for these genes in the formation of NPY-positive and Hcrt-positive (two neuropeptides) neurons, respectively. This has been definitely confirmed thanks to Jorge, a new postdoc who joined the group and took over the project when I left the lab for other horizons. Jorge’s rigorous injections of morpholinos and RNAs and his repeated cell counts again clearly established the functional links between the Lhx transcription factors and the corresponding neuropeptides. Sylvie was so happy, her favorite transcription factor Lhx9 she had discovered in the mouse 20 years ago, was involved in the process of developmental evolution of her favorite animal, the cavefish!

In parallel, we tested the role of Fgf and Shh signaling, pathways well-known to play a role in cavefish brain evolution and eye loss. For these pharmacological experiments, the fact that Astyanax produces hundreds of eggs every morning made this task easier. But what was even better was the chance to work with a cohesive and efficient team to collect, sort and dechorionate the eggs, then to treat them, wash them, fix them, even when it involved working in the middle of the night, for several nights in a row. All the authors of this paper contributed to these pharmacological experiments!

… to behavior evolution

After we had established the link between early signaling, early expression of Lhx genes and differences in neuropeptidergic neuron numbers, Sylvie next encouraged us to complete the story by linking these differences to adaptive behavior observed in cavefish. Honestly, I was not very keen on going down this road, which I thought could be long and difficult. And I was right indeed… it was so hard to get there, especially for Jorge, who worked the most on this and probably suffered a bit. With the behavioral set-up being in a distant building, I think that he had to walk dozens of kilometers to, ironically, demonstrate that the Lhx9-dependant increased number of Hcrt neurons is responsible of hyper locomotion in cavefish. However with the help and the expertise of Yannick, who achieved a level of excellence in behavioral studies on Astyanax, and Cynthia, the engineer responsible for the platform of fish behavior analysis in the Department, problems were solved and we got nice results.

And here we were! We finally got our story, linking the evolution of embryonic development, to neuro-anatomy and behavior. And we got it as a team! Brought together by the trust of Sylvie, and by mutual confidence and friendship: who could ask for more from a postdoctoral experience? I am also very grateful for the opportunity to have contributed to several other papers during this post-doc. Lucie and Jorge are also conducting their own research projects, which will surely benefit from the team spirit in a group where everybody is willing to help the others, and more importantly where everybody feels free to ask for help. As Claude Bernard says: “The idea is the seed; the method is the soil which enables it to develop…” and I believe that teamwork is the best fertilizer helping to yield the best fruits.

(8 votes)

Loading...

This summer, the Company of Biologists, the not-for-profit publisher of Development, is running a Workshop on ‘Development and evolution of the human neocortex‘, organised by Victor Borrell, Wieland Huttner and Arnold Kriegstein.

The Company of Biologists Workshops provide leading experts and early career scientists from a diverse range of scientific backgrounds with a stimulating environment for the cross-fertilisation of interdisciplinary ideas. The programmes are carefully developed and are intended to champion the novel techniques and innovations that will underpin important scientific advances.

There are currently multiple funded spaces for early-career researchers to attend this exciting event (deadline = 23 March). To find out more and apply online please visit

biologists.com/workshops/june2018

(No Ratings Yet)

Loading...

Jun Chen

National Institute of Biological Sciences, Beijing

A discussion of our recent paper: Chen J, Xu N, Wang C, Huang P, Huang H, Jin Z, Yu Z, Cai T, Jiao R, Xi R. Transient Scute activation via a self-stimulatory loop directs enteroendocrine cell pair specification from self-renewing intestinal stem cells. Nat Cell Biol. 2018 Feb;20(2):152-161. doi: 10.1038/s41556-017-0020-0. Epub 2018 Jan 15.

Behind the story

On 2016-5-18, the second day after my first research paper ¹ was published online at my third year of PhD courses, my mentor Rongwen Xi told me to take over the “EEP project”. This project had begun long before I started my PhD courses, and until my participation, has been passed along by three researchers in turn: Na Xu, Pin Huang, and Chenhui Wang; each of them subsequently graduated and moved on with their own academic or industrial paths. Encouraged by my first successful publication, I quickly agreed to take this seemingly never-ending project. I told Dr. Xi a sentence that amused me afterwards, “I won’t give it up until you give up.” This is how this long and tough process begins, and this is also the instant that determines the end of the story.

Introduction

Even as adults, we have stem cells throughout our bodies that are responsible for maintaining many of our tissues. These adult stem cells constantly divide and produce daughter cells, which, through a process called differentiation, become multiple types of mature cells. The fate of the daughter cells can be actively specified by asymmetric cell division, in which cell fate determinants are specifically segregated into one of two stem cell daughter cells ². Alternatively, cell fate can be specified passively; in this case, cells physically depart from the self-renewal niche environment, as with the specification of cystoblasts from Drosophila germline stem cells, and the initiation of differentiation of stem cells in the mouse small intestine upon their departure from the Paneth cell niche ^3,4. Despite several implications from these “renew or differentiate” fate determination events, very little is known about the molecular mechanisms by which distinct, lineage-restricted progenitor cells are generated from a common stem cell pool.

To study this question, we investigated cell fate in a multipotent intestinal stem cell (ISC) experimental model from adult fruit flies. The default mode for cell fate is that ISCs differentiate into enterocytes (EC), which have been shown to occur from approximately 90% of ISC divisions ⁵. However, there is a less-well-understood mode in which ISCs differentiate into pairs of enteroendocrine cells (EEs), which occur from approximately 10% of ISC divisions.

When I started to do this project, previous studies suggested that EEs are directly differentiated from ISCs, implying that the decision of EE specification may occur at the stem cell level in ISCs ^6,7, but how this occurs remains unclear. It has also been revealed that the four-gene cluster acheate-scute complex (As-c) act as EE-fate-determination factors. Furthermore, one of the As-c genes, scute (sc), is both necessary and sufficient for EE specification. Nevertheless, important questions remain about both the molecular and cellular mechanisms through which Sc functions in EE fate decision, and we do not yet know how Sc is regulated in ISCs to control EE fate.

We finally answered these questions in our recent paper, in which we reported that transient activation of Sc determines both the type and number of committed progenitor cells from Drosophila ISCs.

A cell fate is determined by a transiently expressed protein

To better understand the process of EE specification in ISCs, we set up an EE regeneration assay and examined de novo EE regeneration. This assay was first beautifully set up by Na Xu and Pin Huang. Based on the finding that Sc is required for EE generation from ISCs, we temporally knocked down sc starting from the pupal stage, and this process produced flies with midguts lacking EE cells. We then used these EE-less midguts to examine the process of EE production by using temperature shift to re-introduce Sc expression in the midgut. With this assay, we discovered that (i) ISCs actually undergo an initial division to generate a new EE progenitor cell (EEP), and (ii) the EEP then undergoes one final round of cell division to produce a pair of EEs (Figure 2).

To further analyze this two-step cell division process, Chenhui Wang genetically overexpressed sc in ISCs and monitored the cellular events in a time-course experiment. Chenhui found that transient sc expression caused a rapid cell division response, and also induced expression of the EE-marker gene Pros, which is known as a potent cell-cycle inhibitor. These findings and subsequent experiments enable us to precisely define the regulatory circuitry that directs the formation of a pair of EEs from each ISC (Figure 1). Here a concern still exists that we have not given a “seeing is believing” results for cellular events of EE generation because we have not established long-term live imaging technique for fly midgut yet. To solve this problem, I expressed a UAS-RedStinger reporter in sc overexpression system. RedStinger is relatively stable and can serve as a lineage marker to trace the progeny of the originally marked ISCs. The number of cell divisions of the initially labeled ISCs could be deduced based on the mitotic marker PH3 and the number of RedStinger⁺ cells in a single cluster. In this experiment, I observed a tightly ordered  process: The first cell division following sc overexpression occurred in ISCs (PH3+ in a one-cell clone), and at telophase of the first cell division, one of the two daughter cells began to show cytoplasmic Pros accumulation; the second cell division (PH3+ in a two-cell clone) always occurred in the Pros+ daughter cell, that is EEP; the third cell division (PH3+ in a three-cell clone) occurred again in ISCs. These observations suggest that EEs are generated from ISCs via two rounds of cell divisions: an asymmetric division of ISC to generate an EEP, and then the EEP division to produce an EE pair (Figure 3).

Next, to visualize the expression of Sc in midgut, Pin generated a green fluorescent protein (GFP) tagged line for Sc in collaboration with Zhongsheng Yu and Renjie Jiao from the Institute of Biophysics of the Chinese Academy of Sciences. In this line, the GFP was fused to 3’ of the Sc coding region. Initially we were a little bit disappointed as the GFP signal was too weak to visualize and all the researchers had to immunostain with anti-GFP antibody, which effectively amplified the Sc-GFP signal. Immunostaining results revealed that Sc-GFP could be observed in virtually all ISCs but the expression level is largely indistinguishable among ISCs. With improved microscopy technology, I managed to capture GFP signal in unstained samples and found that the Sc-GFP fusion protein is expressed at higher levels in ~15% of the ISCs (Figure 4). This result was exciting because it indicated that Sc may be expressed in a dynamic manner in ISCs, and in a snap shot, you may see a weak expression level in most ISCs, and increased expression levels in a small subset of ISCs.

The next step was to test the cell lineage fate of these Sc^high ISCs. The follow-up cell lineage tracing studies with a Sc-Gal4 line will help to do that, but there was no available Sc-Gal4 line at that time. Fortunately, from 23 (upstream and downstream) glass multiple reporter (GMR) enhancer-GAL4 lines generated for sc, I identified one GAL4 line that drove UAS-GFP expression in some diploid cells in the midgut epithelium. The density (also in ~15% ISCs), distribution, and individual variability of the GFP+ cells were largely similar to those of Sc-GFP+ cells, and about half of RFP reporter driven by this GAL4 line recapitulates Sc-GFP expression, suggesting that this GAL4 line is driven by the enhancer element for sc expression in the midgut. Cell lineage tracing studies with this GAL4 line revealed that the immediate daughter cells of Sc-GAL4⁺ ISCs were mainly EEs; however, these ISCs re-assume their default EC-producing fate once Sc expression is downregulated (Figures 1&5).

The knotty problem

With these exciting new observations, we inevitably faced a mechanistic question, “How does such transient upregulation of Sc in ISCs occur?” This question comes like a boss in video games, and has always been difficult to tackle. Studies over the decades on proneural genes have revealed that the AS-C genes in the neural cell lineages are regulated by highly-complex-cis-regulatory regions, and these regulatory regions are considered to constitute an integrating device for multiple signaling regulators and chromatin factors. Firstly came to our minds was to avoid such “net” and to set out from the reported signals that regulate EE specification in Drosophila midgut. Previous studies suggest that the Slit molecules secreted from EEs activate the Robo2 receptors of ISCs to prevent EE generation, thereby establishing a negative feedback to coordinate EE production with tissue demand. However, Sc expression pattern was unaltered in Robo2 mutants, in which the excessive EE phenotype was prominent. Considering Robo2 activation in ISCs is not sufficient to prevent EE production from ISCs, this mechanism appears to be a modulator rather than a key component in the EE fate decision process. Thus, I had to go back to hit the core of the question, the transcriptional control of As-c genes.

Previous studies on early Drosophila development have suggested reciprocal regulatory relationships between AS-C genes and the enhancer of split complex (E(spl)) genes, which are known as the Notch target genes. Inspired by these reports, I screened a number of candidate reporters for individual E(spl) genes, and identified a single reporter, m8-lacZ, which showed a weak, but similar expression pattern to Sc in wild type guts. To characterize the regulatory relationship between Sc and E(spl)m8, I transiently overexpressed sc in ISCs, and surprisingly saw robust upregulation of m8-lacZ expression in all ISCs. Notably, co-expressing Notch-RNAi did not prevent the upregulation of m8-lacZ expression caused by sc overexpression, suggesting that E(spl)m8 expression is independent of Notch activity in ISCs. To test whether such regulatory relationship similarly applies to other E(spl) genes, I sorted out sc-overexpressed ISCs for mRNA profiling by RNA-seq analysis. Strikingly, in addition to m8, many other E(spl) genes, including m4, m6, m7, mγ, and mδ were strongly upregulated upon sc overexpression. By combining genetic assays and ChIP-seq analysis, we showed Sc could bind to the enhancer regions of many E(spl) genes, and directly upregulate these E(spl) genes in ISCs (Figure 6).

It’s then instinctive to consider whether these E(spl) genes, also known as neural fate repressors, would in turn negatively regulate Sc expression. By combining genetic assays and targeted DamID analysis using a E(spl)m8-Dam fusion line, we showed that E(spl)m8 suppresses sc expression by directly binding to the enhancer region of sc. The direct two-way regulation between Sc and E(spl)m8 form a typical negative feedback regulatory loop, which may explain the transient activation pattern of Sc in ISCs (Figure 6).

The question still has half part unanswered, “how does sc initially build up?” Searching for other transcriptional activators, like other bHLH activators as reported, would make this question a “chick and egg” issue. Interestingly, Sc has been reported to transcriptionally self-stimulate itself, which acts as an essential mechanism for proneural protein accumulation during sensory organ development. To test whether self-stimulation of Sc also occurs in ISCs, we constructed LacZ transcriptional reporter for sc using the Sc-Gal4 enhancer fragment that we had identified. This lacZ reporter was barely detectable in WT midgut epithelium, but effectively induced in ISCs when sc was transiently induced. ChIP-seq data analysis also revealed two Sc binding peaks within this Sc-Gal4 enhancer region (Figure 6). Thus, Sc is able to stimulate its own transcription directly by binding to sc enhancer. Together, our results suggest that two feedback regulatory loops control the transient upregulation of Sc in ISCs prior to EE fate commitment. There is a transcriptional self-stimulation loop that allows Sc to gradually build up and eventually reach a high level to induce EEP specification, and there is a negative feedback regulation loop between Sc and E(spl) genes that returns sc expression back to the baseline level (Figure 1).

The beginning of the end

Given that negative feedback is a common mechanism underlying biochemical oscillations in virtually all organisms, the feedback loops between Sc and E(spl) genes could plausibly be the driver of an oscillatory expression pattern for Sc in ISCs; in theory such oscillatory expression could potentially serve as an internal timer for periodic production of EEs from ISCs. This clock mechanism would be similar to what is known about the circadian clocks, a biological research field that was recently honored with the 2017 Nobel Prize for Physiology or Medicine. We are obviously very excited about the findings and potential implications. However, this is just a tip of iceberg, future cellular and molecular analysis, likely in combination with in vivo live imaging work will allow further testing and refining of the oscillation model proposed in our study, and such experiments will determined whether and how any internal timer is regulated by certain endogenous and/or environmental cues, and whether the oscillation model is generally applicable in other tissue stem cells, including that in humans.

Finally, I want to say that I am very fortunate and grateful to be a part of such a wonderful research team and work on such an exciting project. This work would not be possible without the contribution and help from our past and current lab members, especially Na Xu, Chenhui Wang, and Pin Huang, as well as informaticians Huanwei Huang and Tao Cai at NIBS. I especially want to thank my mentor Dr. Xi for his great guidance and trust, as well as his helpful advice on the writing of this article. As you can imagine, in addition to the “high” moments when the exciting results were first observed, I also had many upset and head-scratching moments during the course of this study. These experiences have endowed me a lot on how to explore, to observe, to cooperate, to write, and to persevere. I believe that no matter how hard it seems like, if you continue to stay focused and think hard, great things may eventually happen, in an instant.

References

1             Chen, J., Xu, N., Huang, H., Cai, T. & Xi, R. A feedback amplification loop between stem cells and their progeny promotes tissue regeneration and tumorigenesis. eLife 5, doi:10.7554/eLife.14330 (2016).

2             Neumuller, R. A. & Knoblich, J. A. Dividing cellular asymmetry: asymmetric cell division and its implications for stem cells and cancer. Genes Dev 23, 2675-2699 (2009).

3             Morrison, S. J. & Spradling, A. C. Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell 132, 598-611 (2008).

4             Li, L. & Xie, T. Stem cell niche: structure and function. Annual review of cell and developmental biology 21, 605-631 (2005).

5             Ohlstein, B. & Spradling, A. Multipotent Drosophila intestinal stem cells specify daughter cell fates by differential notch signaling. Science 315, 988-992 (2007).

6             Zeng, X. & Hou, S. X. Enteroendocrine cells are generated from stem cells through a distinct progenitor in the adult Drosophila posterior midgut. Development 142, 644-653, doi:10.1242/dev.113357 (2015).

7             Biteau, B. & Jasper, H. Slit/Robo signaling regulates cell fate decisions in the intestinal stem cell lineage of Drosophila. Cell reports 7, 1867-1875, doi:10.1016/j.celrep.2014.05.024 (2014).

(4 votes)

Loading...

A few days back over dinner at a CNV gathering, Theresia Gutmann from the Coskun lab casually told me about her PhD work. In collaboration with the Rockefeller University NYC, Theresia had visualized the changing conformation of the human insulin receptor upon insulin binding (paper). I made a sketchnote summarizing their discovery of a conformational switch that could explain how the insulin receptor transforms information about extracellular ligand binding into an intracellular activity to react by taking up glucose!

Original paper Gutmann, Kim et al. (2018): Visualization of ligand-induced transmembrane signaling in the full-length human insulin receptor. Journal of Cell Biology, DOI: 10.1083/jcb.201711047

(3 votes)

Loading...

A postdoc position is available in the Lehoczky Lab (Brigham and Women’s Hospital/Harvard Medical School). The lab is focused on understanding the molecular basis of mouse digit tip regeneration, with the ultimate goal of teasing apart the genetic pathways necessary for this process.  For more information about the lab see LehoczkyLab.org

Applicants with a strong background in regenerative biology, genetics, developmental biology, and/or molecular biology are encouraged to apply. Prior experience with mouse genetics is preferred.  Experience with RNAseq analysis is a plus.

Interested candidates should provide: 1) cv, 2) a brief letter detailing your interest in the lab and relevant past research experience, and 3) contact information for three references who can comment on your research

Application materials and any questions regarding the position should be sent to Jessica: jlehoczky@bwh.harvard.edu

(No Ratings Yet)

Loading...

Our latest monthly trawl for developmental biology (and other cool) preprints. Let us know if we missed anything.

On February 20^th, The Company of Biologists launched preLights, a community-led preprint highlighting service. A panel of early career researchers (the ‘preLighters’) select and comment on recent preprints that caught their eye, and encourage preprint authors to answer any questions about the work that they had. So far it looks great, and the developmental biology content has been especially good (see the dedicated subject category). We’d love to know what you think: you can contact the team via the site or the Twitter feed.

The idea behind the site was influenced in part by this list – as it got longer and longer (reflecting increased preprint usage), we were wondering how else we could encourage and promote the discussion of preprints, and the preLights idea took form. Rest assured that this list will live on, at least until the point at which it gets impossibly long!

And here’s the list – all the developmental biology I could find, plus relevant and cool other preprints thrown in for good measure.

The preprints were hosted on bioRxiv, PeerJ, and arXiv. Use these links to get to the section you want:

Developmental biology

| Patterning & signalling

| Morphogenesis & mechanics

| Genes & genomes

| Stem cells, regeneration & disease modelling

Evo-devo & evo

Cell biology

Modelling

Tools & resources

| Imaging etc.

| Genome tools

Research practice & education

Why not…

Developmental biology

| Patterning & signalling

Human axial progenitors generate trunk neural crest cells. Thomas J.R. Frith, Ilaria Granata, Erin Stout, Matthew Wind, Oliver Thompson, Katrin Neumann, Dylan Stavish, Paul R Heath, James O.S. Hackland, Konstantinos Anastassiadis, Mina Gouti, James Briscoe, Valerie Wilson, Mario R Guarracino, Peter W Andrews, Anestis Tsakiridis

Lineage tracing axial progenitors using Nkx1.2CreERT2 mice defines their trunk and tail contributions. Aida Rodrigo Albors, Pamela A Halley, Kate G Storey

A conserved regulatory program drives emergence of the lateral plate mesoderm. Christopher Hess, Karin Dorien Prummel, Susan Nieuwenhuize, Hugo Parker, Katherine W. Rogers, Iryna Kozmikova, Claudia Racioppi, Sibylle Burger, Eline C. Brombacher, Alexa Burger, Anastasia Felker, Elena Chiavacci, Gopi Shah, Jan Huisken, Zbynek Kozmik, Lionel Christiaen, Patrick Mueller, Marianne Bronner, Robb Krumlauf, Christian Mosimann

Hedgehog signaling controls progenitor differentiation timing during heart development. Megan Rowton, Andrew D. Hoffmann, Jeffrey D. Steimle, Xinan Holly Yang, Alexander Guzzetta, Sonja Lazarevic, Chul Kim, Nikita Deng, Emery Lu, Jessica Jacobs-Li, Shuhan Yu, Erika Hanson, Carlos Perez-Cervantes, Sunny Sun-Kin Chan, Kohta Ikegami, Daniel J. Garry, Michael Kyba, Ivan P. Moskowitz

SOX2 Regulation by Hedgehog Signaling Controls Adult Lingual Epithelium Homeostasis. David Castillo-Azofeifa, Kerstin Seidel, Lauren Gross, Belkis Jacquez, Ophir D Klein, Linda A. Barlow

Extracellular Pax6 regulates tangential Cajal-Retzius cell migration. Hadhemi Kaddour, Eva Coppola, Ariel Di Nardo, Andrea Wizenmann, Michel Volovitch, Alain Prochiantz, Alessandra Pierani

Axon Guidance Signaling Modulates Epithelial to Mesenchymal Transition in Stem Cell-Derived Retinal Pigment Epithelium. Srinivas R. Sripathi, Melissa M. Liu, Ming-Wen Hu, Jun Wan, Jie Cheng, Yukan Duan, Joseph Mertz, Karl Wahlin, Julien Maruotti, Cynthia A Berlinicke, Jiang Qian, Donald J. Zack

Neuroligins mediate presynaptic maturation through brain-derived neurotrophic factor signaling. Andoniya Petkova, Nina Goedecke, Martin Korte, Thomas Dresbach

In vivo clonal analysis reveals spatiotemporal regulation of thalamic nucleogenesis. Samuel Wong, Earl Parker Scott, Wenhui Mu, Xize Guo, Ella Borgenheimer, Madeline Freeman, Guo-li Ming, Qing-Feng Wu, Hongjun Song, Yasushi Nakagawa

Osteoclasts control sensory neurons axonal growth through epidermal growth factor receptor signaling. Estrela Neto, Daniela Sousa, Francisco Conceição, Luís Leitão, Cecília Juliana Alves, Inês Alencastre, Jonathan West, Richard O. C. Oreffo, Meriem Lamghari

FGF activity asymmetrically regulates the timing of habenular neurogenesis in a Nodal-dependent manner. Benjamin J Dean, Joshua T Gamse, Shu-Yu Wu

The transcription factor Tfap2e/AP-2ε plays a pivotal role in maintaining the identity of basal vomeronasal sensory neurons. Jennifer M Lin, Ed Zandro M Taroc, Jesus A Frias, Aparna Prasad, Allison N Catizone, Morgan A Sammons, Paolo E. Forni

Tdrd6a regulates the aggregation of Buc into functional subcellular compartments that drive germ cell specification. Elke F Roovers, Lucas JT Kaaij, Stefan Redl, Alfred W Bronkhorst, Kay Wiebrands, Antonio Miguel de Jesus Domingues, Hsin-Yi Huang, Chung-Ting Han, Willi Salvenmoser, Dominic Gruen, Falk Butter, Alexander van Oudenaarden, Rene F Ketting

Blimp-1 mediates the temporal control of embryonic tube maturation. Arzu Ozturk-Colak, Camille Stephan-Otto Attolini, Jordi Casanova, Sofia J. Araujo

The integrated stress response regulates BMP signaling through effects on translation. Elke Malzer, Caia S Dominicus, Joseph E Chambers, Souradip Mookerjee, Stefan J Marciniak

Dietary lipids modulate Notch signaling and influence adult intestinal development and metabolism in Drosophila. Rebecca Obniski, Matthew Sieber, Allan C Spradling

Spatio-temporal relays control layer specificity of motion-direction sensitive neurons in Drosophila. Holger Apitz, Iris Salecker

Torso-like is a component of the hemolymph and regulates the insulin signalling pathway in Drosophila. Michelle A Henstridge, Lucinda Aulsebrook, Takashi Koyama, Travis K Johnson, James C Whisstock, Tony Tiganis, Christen K Mirth, Coral G Warr

Variability in timing of a β-catenin pulse biases a stochastic cell fate decision in C. elegans. Jason R Kroll, Jasonas Tsiaxiras, Jeroen S van Zon

The Atypical Rho GTPase CHW-1 Works With SAX-3/Robo to Mediate Axon Guidance in Caenorhabditis elegans. Jamie Alan, Sara Robinson, Katie Magsig, Rafael Demarco, Erik A. Lundquist

Phospho-regulation of Atoh1 is required for plasticity of secretory progenitors and tissue regeneration. Goran Tomic, Edward Morrissey, Sarah Kozar, Shani Ben-Moshe, Alice Hoyle, Roberta Azzarelli, Richard Kemp, Chandra Sekhar Reddy Chilamakuri, Shalev Itzkovitz, Anna Philpott, Douglas Winton

The TMEM16A Channel Mediates the fast polyspermy block in Xenopus Laevis. Katherine L Wozniak, Wesley A Phelps, Maiwase Tembo, Miler T Lee, Anne E Carlson

Early lethality of embryos derived from transgenic Xenopus females is associated with reduced ovarian grem1 expression. Caroline W Beck, Joanna Ward, Lisa Troise, Catherine Brochard

Genetic inactivation of alpha-synuclein affects embryonic development of dopaminergic neurons of the substantia nigra but not the ventral tegmental area in mouse brain. Tatyana V Tarasova, Olga A Lytkina, Valeria V Goloborshcheva, Larisa N Skuratovskaya, Alexandr I Antohin, Ruslan K Ovchinnikov, Michail S Kukharsky​

Single-cell analysis of progenitor cell dynamics and lineage specification of the human fetal kidney. Rajasree Menon, Edgar A. Otto, Austin Kokoruda, Jian Zhou, Zidong Zhang, Euisik Yoon, Yu-Chih Chen, Olga Troyanscaya, Jason Spence, Matthias Kretzler, Cristina Cebrian

A hypomorphic Stip1 allele reveals the requirement for chaperone networks in mouse development and aging. Rachel Lackie, Marilene H Lopes, Sali M.K. Farhan, Abdul Razzaq, Gilli Moshitzky, Mariana B Prado, Flavio H Beraldo, Andrzej Maciejewski, Robert Gros, Jue Fan, Wing-Yiu Choy, David Greenberg, Vilma R Martins, Martin Duennwald, Hermona Soreq, Vania F Prado, Marco A. M. Prado

Bioelectric-calcineurin signaling module regulates allometric growth and size of the zebrafish fin. Jacob Daane, Jennifer Lanni, Ina Rothenberg, Guiscard Seebohm, Charles Higdon, Stephen Johnson, Matthew Harris

GEMC1 and CCNO are required for efferent duct development and male fertility. Berta Terre, Michael Lewis, Gabriel Gil-Gomez, Travis H Stracker

| Morphogenesis & mechanics

Characterization of convergent thickening, a major convergence force producing morphogenic movement in amphibians. David R Shook, Jason Wen, Ana Rolo, Brian Francica, Destiny Dobins, Paul Skoglund, Douglas DeSimone, Rudolf Winklbauer, Ray Keller

Large, long range tensile forces drive convergence during Xenopus blastopore closure and body axis elongation. David R Shook, Ray Keller, Lance Davidson, Eric M. Kasprowicz

Contact-dependent cell communications drive morphological invariance during ascidian embryogenesis. Leo Guignard, Ulla-Maj Fiuza, Bruno Leggio, Emmanuel Faure, Julien Laussu, Lars Hufnagel, Gregoire Malandain, Christophe Godin, Patrick Lemaire

Tbx1 regulates extracellular matrix- and cell-cell interactions in the second heart field. Antonio Baldini, Daniela Alfano, Alessandra Altomonte, Marchesa Bilio

An unconventional myosin, myosin 1d regulates Kupffer’s vesicle morphogenesis and laterality. Manush Saydmohammed, Hisato Yagi, Michael Calderon, Madeline J Clark, Timothy Feinstein, Ming Sun, Donna B Stolz, Simon C Watkins, Jeffrey Amack, Cecilia Lo, Michael Tsang

Myosin1D is an evolutionarily conserved determinant of animal Left/Right asymmetry. Thomas Juan, Charles Géminard, Jean-Baptiste Coutelis, Delphine Cerezo, Sophie Polès, Stéphane Noselli, Maximilian Fürthauer

Integrin signaling downregulates filopodia in muscle-tendon attachment. Benjamin Richier, Yoshiko Inoue, Ulrich Dobramysl, Jonathan Friedlander, Nicholas H. Brown, Jennifer Louise Gallop

Long-range Notch-mediated tissue patterning requires actomyosin contractility. Ginger Hunter, Li He, Norbert Perrimon, Guillaume Charras, Edward Giniger, Buzz Baum

Atf3 links loss of epithelial polarity to defects in cell differentiation and cytoarchitecture. Colin D. Donohoe, Gabor Csordas, Andreia Correia, Marek Jindra, Corinna Klein, Bianca Habermann, Mirka Uhlirova

Myosin Heavy Chain-embryonic is a crucial regulator of skeletal muscle development and differentiation. Akashi Sharma, Megha Agarwal, Amit Kumar, Pankaj Kumar, Masum Saini, Gabrielle Kardon, Sam Mathew

The C. elegans heterochronic gene lin-28 coordinates the timing of hypodermal and somatic gonadal programs for hermaphrodite reproductive system morphogenesis. Sungwook Choi, Victor Ambros

Non-canonical apical constriction shapes emergent matrices in C. elegans. Sophie S Katz, Chloe Maybrun, Alison Renee Frand

A microtubule-based mechanism predicts cell division orientation in plant embryogenesis. Bandan Chakrabortty, Viola Willemsen, Thijs de Zeeuw, Che-Yang Liao, Dolf Weijers, Bela Mulder, Ben Scheres

Feeling the force: how pollen tubes deal with obstacles. Jan T Burri, Hannes Vogler, Nino F Läubli, Chengzhi Hu, Ueli Grossniklaus, Bradley J Nelson

Microtubule-associated protein IQ67 DOMAIN5 regulates interdigitation of leaf pavement cells in Arabidopsis thaliana. Dipannita Mitra, Pratibha Kumari, Jakob Quegwer, Sandra Klemm, Birgit Moeller, Yvonne Poeschl, Paul Pflug, Gina Stamm, Steffen Abel, Katharina Bürstenbinder

Cell death in cells overlying lateral root primordia contributes to organ growth in Arabidopsis. Sacha Escamez, Benjamin Bollhoner, Hardy Hall, Domenique Andre, Beatrice Berthet, Ute Voss, Amnon Lers, Alexis Maizel, Malcolm Bennett, Hannele Tuominen

FERONIA’s sensing of cell wall pectin activates ROP GTPase signaling in Arabidopsis. Wenwei Lin, Wenxin Tang, Charles Anderson, Zhenbiao Yang

Adaptive diversification of growth allometry in the plant Arabidopsis thaliana. Francois Vasseur, Moises Exposito-Alonso, Oscar Javier Ayala-Garay, George Wang, Brian J Enquist, Denis Vile, Cyrille Violle, Detlef Weigel

A mechanism for the proliferative control of tissue mechanics in the absence of growth. Min Wu, Madhav Mani

Endothelia extrude apoptotic cells to maintain a constant barrier. Tara Mleynek, Dean Li, Jody Rosenblatt, Michael Jarman Redd, Aubrey Chan, Yapeng Gu

Cellular Migration May Exhibit Intrinsic Left-Right Asymmetries: A meta-analysis. Kelly G. Sullivan, Laura N. Vandenberg, Michael Levin

Increased prenatal brain growth in a transgenic mouse model decreases cranial development: An expensive tissue hypothesis for the skull. Elisabeth K N López​, Matthew J Ravosa

In vivo optochemical control of cell contractility at single cell resolution by Ca2+ induced myosin activation. Deqing Kong, Fred Wolf, Joerg Grosshans.

A quantitative study of blood circulation in the developing adult ascidian tunicate Ciona savignyi (Cionidae). Michael W Konrad

Tissue-specific activities of the Fat1 cadherin cooperate to control neuromuscular morphogenesis. Francoise Helmbacher

Zebrafish sp7 mutants show tooth cycling independent of attachment, eruption and poor differentiation of teeth. Erika Kague, Paul Eckhard Witten, Mieke Soenens, Camila Lovaglio Campos, Tiago Lubiana, Shannon Fisher, Chrissy Hammond, Kate Robson Brown, Maria Rita Passos Bueno, Ann Huysseune

| Genes & genomes

Disruption in A-to-I editing levels affects C. elegans development more than a complete lack of editing. Nabeel S. Ganem, Noa Ben-Asher, Aidan C. Manning, Sarah N. Deffit, Michael C. Washburn, Emily C. Wheeler, Gene W Yeo, Orna Ben-Naim Zgayer, Einav Mantsur, Heather A. Hundley, Ayelet T Lamm

ADAR1 A-to-I RNA editing alters codon usage. Pavla Brachova, Nehemiah S Alvarez, Xiaoman Hong, Kailey A. Vincent, Keith E. Latham, Lane K. Christenson

Identification of piRNA binding sites reveals the Argonaute regulatory landscape of the C. elegans germline. En-Zhi Shen, Hao Chen, Ahmet R. Ozturk, Shikui Tu, Masaki Shirayama, Wen Tang, Yue-He Ding, Si-Yuan Dai, Zhiping Weng, Craig C. Mello

H3K9 methylation maintains female identity in Drosophila germ cells through repression of the spermatogenesis program. Anne Smolko, Laura Shapiro-Kulnane, Helen Salz

Fanconi Anemia FANCM/FNCM-1 and FANCD2/FCD-2 are required for maintaining histone methylation levels and interact with the histone demethylase LSD1/SPR-5 in C. elegans. Hyun-Min Kim, Sara E Beese-Sims, Monica P. Colaiácovo

GTSF-1 is required for the formation of a functional RNA-dependent RNA Polymerase complex in C. elegans. Miguel V. Almeida, Sabrina Dietz, Stefan Redl, Emil Karaulanov, Andrea Hildebrandt, Christian Renz, Helle D. Ulrich, Julian König, Falk Butter, René F. Ketting

Dissection of the microProtein miP1 floral repressor complex in Arabidopsis. Vandasue L. Rodrigues, Ulla Dolde, Daniel Straub, Tenai Eguen, Esther Botterweg-Paredes, Bin Sun, Shinyoung Hong, Moritz Graeff, Man-Wah Li, Joshua Gendron, Stephan Wenkel

Differences in firing efficiency, chromatin and transcription underlie the developmental plasticity of Arabidopsis originome. Joana Sequeira-Mendes, Zaida Vergara, Ramon Peiro, Jordi Morata, Irene Araguez, Celina Costas, Raul Mendez-Giraldez, Josep Casacuberta, Ugo Bastolla, Crisanto Gutierrez

Incomplete reprogramming of cell-specific epigenetic marks during asexual reproduction leads to heritable phenotypic variation in plants. Anjar Wibowo, Claude Becker, Julius Durr, Jonathan Price, Stijn Staepen, Sally Hilton, Hadi Putra, Ranjith Papareddy, Quentin Saintain, Sarah Harvey, Gary D Bending, Paul Schulze-Lefert, Detlef Weigel, Jose Gutierrez-Marcos

Epigenomic plasticity of Arabidopsis msh1 mutants under prolonged cold stress. Sunil Kumar Kenchanmane Raju, Mon-Ray Shao, Yashitola Wamboldt, Sally Mackenzie

A Lotus japonicus E3 ligase interacts with the Nod factor receptor 5 and positively regulates nodulation. Daniela Tsikou, Estrella E. Ramirez, Ioanna S Psarrakou, Jaslyn E Wong, Dorthe B Jensen, Erika Isono, Simona Radutoiu, Kalliope K Papadopoulou

Dazl regulates germ cell survival through a network of polyA proximal mRNA interactions. Leah L Zagore, Thomas J Sweet, Molly M Hannigan, Sebastien M Weyn-Vanhentenryck, Chaolin Zhang, Donny D Licatalosi

Enhancer RNAs are necessary and sufficient for activity-dependent neuronal gene transcription. Nancy V.N. Gallus, Rhiana A. Simon, Aaron J Salisbury, Jasmin S. Revanna, Kendra D. Bunner, Katherine E. Savell, Faraz A. Sultan, Charles A. Gersbach, Jeremy J. Day

Mef-2 and p300 interact to regulate expression of the homeostatic regulator Pumilio in Drosophila. Wei-Hsiang Lin, Richard Baines

APC/C-Vihar regulates centrosome activity and stability in the Drosophila germline. Alexis L. Braun, Francesco Meghini, Gema Villa-Fombuena, Elisa M. Fernandez, Morgane Guermont, David M Glover, Maria D. Martin-Bermudo, Acaimo Gonzalez-Reyes, Yuu Kimata

A Genetic Program Mediates Cold-warming Response and Promotes Stress-induced Phenoptosis in C. elegans. Wei Jiang, Yuehua Wei, Yong Long, Arthur Owen, Bingying Wang, Xuebing Wu, Shuo Luo, Yongjun Dang, Dengke K. Ma

DNA methylation dynamics during embryonic development and postnatal maturation of the mouse auditory organ of Corti. Ofer Yizhar-Barnea, Cristina Valensisi, Kamal Kishore, Naresh Doni Jayavelu, Colin Andrus, Tal Koffler-Brill, Kathy Ushakov, Kobi Perl, Yael Noy, Yoni Bhonker, Mattia Pelizzola, R. David Hawkins, Karen B. Avraham

Aggregation recovers developmental plasticity in mouse polyploid embryos. Hiroyuki Imai, Wataru Fujii, Ken Takeshi Kusakabe, Yasuo Kiso, Kiyoshi Kano

Capturing the onset of PRC2-mediated repressive domain formation. Ozgur Oksuz, Varun Narendra, Chul-Hwan Lee, Nicolas Descostes, Gary LeRoy, Ramya Raviram, Lili Blumenberg, Kelly Karch, Pedro R. Rocha, Benjamin A. Garcia, Jane A. Skok, Danny Reinberg

Cell type-dependent control of p53 transcription and enhancer activity by p63. Gizem Karsli Uzunbas, Faraz Ahmed, Morgan A Sammons

Genome-wide enhancer – gene regulatory maps in two vertebrate genomes. Yves Clément, Patrick Torbey, Pascale Gilardi-Hebenstreit, Hugues Roest Crollius

KLF6 and STAT3 co-occupy regulatory DNA and functionally synergize to promote axon growth in CNS neurons. Zimei Wang, Ishwariya Venkatesh, Vatsal Mehra, Matthew Simpson, Brian Maunze, Erik Eastwood, Lyndsey Holan, Murray Blackmore

Germline DNA replication timing shapes mammalian genome composition. Yishai Yehida, Britny Blumenfeld, Nina Mayorek, Kirill Makedonski, Oriya Vardi, Yousef Mansour, Hagit Masika, Marganit Farago, Shulamit Baror-Sebban, Yosef Buganim, Amnon Koren, Itamar Simon

| Stem cells, regeneration & disease modelling

Tracing the Transitions from Pluripotency to Germ Cell Fate with CRISPR Screening. Jamie A Hackett, Yun Huang, Ufuk Gunesdogan, Kristjan Holm-Gretarsson, Toshihiro Kobayashi, Azim M Surani

Neutralizing Gatad2a-Chd4-Mbd3 Axis within the NuRD Complex Facilitates Deterministic Induction of Naive Pluripotency. Nofar Mor, Yoach Rais, Shani Peles, Daoud Sheban, Alejandro Aguilera-Castrejon, Asaf Zviran, Dalia Elinger, Sergey Viukov, Shay Geula, Vladislav Krupalnik, Mirie Zerbib, Elad Chomsky, Lior Lasman, Tom Shani, Jonathan Bayerl, Ohad Gafni, Suhair Hanna, Jason Buenrostro, Tzachi Hagai, Hagit Masika, Yehudit Bergman, William J. Greenleaf, Miguel A. Esteban, Yishai Levin, Rada Massarwa, Yifat Merbl, Noa Novershtern, Jacob H. Hanna

Delayed activation of the DNA replication licensing system in Lgr5(+) intestinal stem cells. Thomas Carroll, Ian Newton, Yu Chen, Julian J. Blow, Inke Nathke

Efficient differentiation of vascular endothelial cells from dermal-derived mesenchymal stem cells induced by endothelial cell lines conditioned medium. Ling Zhou, Xuping Niu, Jiannan Liang, Junqin Li, Jiao Li, Yueai Cheng, Yanfeng Meng, Qiang Wang, Xiaoli Yang, Gang Wang, Yu Shi, Erle Dang, Kaiming Zhang

Clonal Level Lineage Commitment Pathways of Hematopoietic Stem Cells In Vivo. Rong Lu, Agnieszka Czechowicz, Jun Seita, Du Jiang, Irving L Weissman

Hematopoietic Stem And Progenitor Cells Use Podosomes To Transcellularly Home To The Bone Marrow. Timo Rademakers, Marieke Goedhart, Mark Hoogenboezem, Alexander García Ponce, Jos van Rijssel, Maryna Samus, Michael Schnoor, Stefan Butz, Stephan Huveneers, Dietmar Vestweber, Martijn A Nolte, Carlijn Voermans, Jaap D van Buul

Epigenetic aging of human hematopoietic cells is not accelerated upon transplantation into mice. Joana Frobel, Susann Rahmig, Julia Franzen, Claudia Waskow, Wolfgang Wagner

Emergence of the erythroid lineage from multipotent hematopoiesis. Betsabeh Khoramian Tusi, Samuel L Wolock, Caleb Weinreb, Yung Hwang, Daniel Hidalgo, Rapolas Zilionis, Ari Waisman, Jun Huh, Allon M Klein, Merav Socolovsky

An immortalised mesenchymal stem cell line maintains mechano-responsive behaviour and can be used as a reporter of substrate stiffness. Asier Galarza Torre, Joshua E Shaw, Amber Wood, Hamish T J Gilbert, Oana Dobre, Paul Genever, Keith Brennan, Stephen M Richardson, Joe Swift

Heat shock induces the depletion of Oct4 in mouse blastocysts and stem cells. Mo-bin Cheng, Xue Wang, Yue Huang, Ye Zhang

Single-cell transcriptome of antler stem cells from antlerogenic periosteum. Hengxing Ba, Datao Wang, Weiyao Wu, Hongmei Sun, Chunyi Li

Xist Intron 1 Repression by TALE Transcriptional Factor Improves Somatic Cell Reprogamming in Mice. Jindun Zhang, Xuefei Gao, Jian Yang, Xiaoying Fan, Wei Wang, Yanfeng Liang, Lihong Fan, Hongmei Han, Xiaorong Xu, Fuchou Tang, Siqin Bao, Pentao Liu, Xihe Li

Tectal stem cells display diverse regenerative capacities. Benjamin W Lindsey, Georgia E Aitken, Jean K Tang, Mitra Khabooshan, Celia Vandestadt, Jan Kaslin

Developmental chromatin restriction of pro-growth gene networks acts as an epigenetic barrier to axon regeneration in cortical neurons. Ishwariya Venkatesh, Vatsal Mehra, Zimei Wang, Ben Califf, Murray Blackmore

Neuregulin-1 exerts molecular control over axolotl lung regeneration through ErbB family receptors. Tyler B Jensen, Peter Giunta, Natalie Grace Schulz, Yaa Kyeremateng, Hilary Wong, Adeleso Adesina, James R Monaghan

Targeting TrkB with a brain-derived neurotrophic factor mimetic promotes myelin repair in the brain. Jessica Louise Fletcher, Rhiannon J Wood, Jacqueline Nguyen, Eleanor ML Normon, Christine MK Jun, Alexa R Prawdiuk, Melissa Biemond, Huynh TH Nguyen, Susan E Northfield, Richard A Hughes, David G Gonsalvez, Junhua Xiao, Simon S Murray

Age-dependent dormant resident progenitors are stimulated by injury to regenerate Purkinje neurons. Nermin Sumru Bayin, Alexandre Wojcinski, Aurelien Mourton, Hiromitsu Saito, Noboru Suzuki, Alexandra L Joyner

Reversing Glial Scar Back To Neural Tissue Through NeuroD1-Mediated Astrocyte-To-Neuron Conversion. Lei Zhang, Zhuofan Lei, Ziyuan Guo, Zifei Pei, Yuchen Chen, Fengyu Zhang, Alice Cai, Yung Kin Mok, Grace Lee, Vishal Swaminathan, Fan Wang, Yuting Bai, Gong Chen

Loss of embryonic neural crest cardiomyocytes causes adult hypertrophic cardiomyopathy. Sarah Abdul-Wajid, Bradley Demarest, H. Joseph Yost

p53 deletion rescues apoptosis and microcephaly in a Kif20b mouse mutant. Jessica Neville Little, Noelle D. Dwyer

Altered neocortical gene expression, brain overgrowth and functional over-connectivity in Chd8 haploinsufficient mice. Philipp Suetterlin, Shaun Hurley, Conor Mohan, Kimberley L. H. Riegman, Marco Pagani, Angela Caruso, Jacob Ellegood, Alberto Galbusera, Ivan Crespo-Enriquez, Caterina Michetti, Yohan Yee, Robert Ellingford, Olivier Brock, Alessio Delogu, Philippa Francis-West, Jason P. Lerch, Maria Luisa Scattoni, Alessandro Gozzi, Cathy Fernandes, Albert Basson

Survey of human chromosome 21 gene expression effects on early development in Danio rerio. Sarah Edie, Norann A Zaghloul, Carmen C Leitch, Donna K Klinedinst, Janette Lebron, Joey F Thole, Andrew S. McCallion, Nicholas Katsanis, Roger H. Reeves

Regulation of midgut cell proliferation impacts Aedes aegypti susceptibility to dengue virus. Mabel L. Taracena, Vanessa Bottino-Rojas, Octavio A.C. Talyuli, Ana Beatriz Walter-Nuno, Jose Henrique M. Oliveira, Yesseinia I. Anglero-Rodriguez, Michael B. Wells, George Dimopoulos, Pedro L. Oliveira, Gabriela O. Paiva-Silva

Ablation of Ezh2 in neural crest cells leads to Hirschsprung’s disease-like phenotype in mice. Joomyeong Kim, Hana Kim, Ingeborg M. Langohr, Mohammad Faisal, Margaret McNulty, Caitlin Thorn

Building a schizophrenia genetic network: Transcription Factor 4 regulates genes involved in neuronal development and schizophrenia risk. Hanzhang Xia, Fay M Jahr, Nak-Kyeong Kim, Linying Xie, Andrey A Shabalin, Julien Bryois, Douglas H Sweet, Mohamad M Kronfol, Preetha Palasuberniam, MaryPeace McRae, Brien P Riley, Patrick F Sullivan, Edwin J van den Oord, Joseph McClay

Pervasive epistasis modulates neurodevelopmental defects of the autism-associated 16p11.2 deletion. Janani Iyer, Mayanglambam Dhruba Singh, Matthew Jensen, Payal Patel, Lucilla Pizzo, Emily Huber, Haley Koerselman, Alexis T. Weiner, Paola Lepanto, Komal Vadodaria, Alexis Kubina, Qingyu Wang, Abigail Talbert, Sneha Yennawar, Jose Badano, J. Robert Manak, Melissa M. Rolls, Arjun Krishnan, Santhosh Girirajan

The critical role of ASD-related gene CNTNAP3 in regulating synaptic development and social behavior in mice. Dali Tong, Ruiguo Chen, Yulan Lu, Weike Li, Yuefang Zhang, Junkai Lin, Lingjie He, Ting Dang, Shifang Shan, Xiaohong Xu, Yi Zhang, Chen Zhang, Yasong Du, Wen-Hao Zhou, Xiaoqun Wang, Zilong Qiu

Haploinsufficiency of autism candidate gene NUAK1 impairs cortical development and behavior. Virginie Courchet, Amanda J Roberts, Peggy Del Carmine, Tommy L Lewis Jr., Franck Polleux, Julien Courchet

The dyslexia susceptibility KIAA0319 gene shows a highly specific expression pattern during zebrafish development supporting a role beyond neuronal migration. Monika Gostic, Angela Martinelli, Carl Tucker, Zhengyi Yang, Federico Gasparoli, Kishan Dholakia, Keith Sillar, Javier Tello, Silvia Paracchini

Accelerated brain aging towards transcriptional inversion in a zebrafish model of familial Alzheimer’s disease. Nhi Hin, Morgan Newman, Jan Kaslin, Alon M. Douek, Amanda Lumsden, Xin-Fu Zhou, Noralyn B. Mañucat-Tan, Alastair Ludington, David L. Adelson, Stephen Pederson, Michael Lardelli

Ratiometric assays of autophagic flux in zebrafish for analysis of familial Alzheimer’s disease-like mutations. Haowei Jiang, Morgan Newman, Dhanushika Ratnayake, Michael Lardelli

Increased autophagy in ephrinB2 deficient osteocytes is associated with hypermineralized, brittle bones. Christina Vrahnas, Toby A Dite, Niloufar Ansari, Blessing Crimeen-Irwin, Huynh Nguyen, Mark R Forwood, Yifang Hu, Mika Ikegame, Keith R Bambery, Cyril Petibois, Mark J Tobin, Gordon K Smyth, Jonathan S Oakhill, T John Martin, Natalie A Sims

Evo-devo & evo

Divergent genetic mechanisms lead to spiny hair in mammals. Gislene L. Goncalves, Renan Maestri, Gilson R.P. Moreira, Marly A.M. Jacobi, Thales R.O. Freitas, Hopi E. Hoekstra

Endoderm Morphogenesis Reveals Integration of Distinct Processes in the Development and Evolution of Pharyngeal Arches. Shinji Takada, Kazunori Okada, Hiroshi Wada

Developmental Mechanisms Linking Form and Function During Jaw Evolution. Katherine C Woronowicz, Stephanie E Gline, Safa T Herfat, Aaron J Fields, Richard A Schneider

An evolutionary-conserved Wnt3/β-catenin/Sp5 feedback loop restricts head organizer activity in Hydra. Matthias Christian Vogg, Leonardo Beccari, Laura Iglesias Olle, Christine Rampon, Sophie Vriz, Chrystelle Perruchoud, Yvan Wenger, Brigitte Galliot

tarsal-less is expressed as a gap gene but has no gap gene phenotype in the moth midge Clogmia albipunctata. eva jimenez-guri, Karl Wotton, Johannes Jaeger

Evidence of adhesion and signaling roles for β-catenin in the sponge Ephydatia muelleri. Klaske J. Schippers, Scott A. Nichols

From spiral cleavage to bilateral symmetry: The developmental cell lineage of the annelid brain. Pavel Vopalensky, Maria Antonietta Tosches, Kaia Achim, Mette Handberg-Thorsager, Detlev Arendt

Elongation during segmentation shows axial variability, low mitotic rates, and synchronized cell cycle domains in the crustacean, Thamnocephalus platyurus. Savvas J Constantinou, Nicole Duan, Ariel D. Chipman, Lisa M. Nagy, Terri A. Williams

Changes in the neuropeptide complement correlate with nervous system architectures in xenacoelomorphs. Daniel Thiel, Mirita Franz-Wachtel, Felipe Aguilera, Andreas Hejnol

Intergenerational epigenetic inheritance in reef-building corals. Yi Jin Liew, Emily J. Howells, Xin Wang, Craig T. Michell, John A. Burt, Youssef Idaghdour, Manuel Aranda

Expanding the genetic toolkit of Tribolium castaneum. Johnathan C Rylee, Dylan J Siniard, Kaitlin Doucette, Gabriel E Zentner, Andrew Zelhof

Convergent evolution of gene expression in two high-toothed stickleback populations. James C Hart, Nicholas A Ellis, Michael B Eisen, Craig T Miller

Identification of general patterns of sex-biased expression in Daphnia, a genus with environmental sex determination. Cécile Molinier, Céline Reisser, Peter Fields, Adeline Segard, Yan Galimov, Christoph R. Haag

Genomic imprinting mediates dosage compensation in a young plant XY system. Aline Muyle, Niklaus Zemp, Cecile Fruchard, Radim Cegan, Jan Vrana, Clothilde Deschamps, Raquel Tavares, Franck Picard, Roman Hobza, Alex Widmer, Gabriel Marais

Delegating sex: differential gene expression in stolonizing syllids uncovers the hormonal control of reproduction in Annelida. Patricia Alvarez-Campos, Nathan Kenny, Aida Verdes, Rosa Maria Fernandez, Marta Novo, Gonzalo Giribet, Ana Riesgo

Concurrent duplication of the Cid and Cenp-C genes in the Drosophila subgenus with signatures of subfunctionalization and male germline-biased expression. Jose R. Teixeira, Guilherme B. Dias, Marta Svartman, Alfredo Ruiz, Gustavo C. S. Kuhn

Convergent regulatory evolution and the origin of flightlessness in palaeognathous birds. Timothy B. Sackton, Phil Grayson, Alison Cloutier, Zhirui Hu, Jun S. Liu, Nicole E. Wheeler, Paul P. Gardner, Julia A. Clarke, Allan J. Baker, Michele Clamp, Scott V. Edwards

Genotyping-by-sequencing supports a genetic basis for alpine wing-reduction in a New Zealand stonefly. Andrew J. Veale, Brodie J. Foster, Peter K. Dearden, Jon M. Waters

Transposable elements generate regulatory novelty in a tissue specific fashion. Marco Trizzino, Aurelie Kapusta, Christopher Brown

The effects of haploid selection on Y chromosome evolution in a dioecious plant. George Sandler, Felix E.G. Beaudry, Spencer C.H. Barrett, Stephen I. Wright

Adaptive Reduction of Male Gamete Number in a Selfing Species. Takashi Tsuchimatsu, Hiroyuki Kakui, Misako Yamazaki, Cindy Marona, Hiroki Tsutsui, Afif Hedhly, Dazhe Meng, Yutaka Sato, Thomas Stadler, Ueli Grossniklaus, Masahiro M. Kanaoka, Michael Lenhard, Magnus Nordborg, Kentaro K. Shimizu

Firefly genomes illuminate parallel origins of bioluminescence in beetles. Timothy R Fallon, Sarah E Lower, Ching-Ho Chang, Manabu Bessho-Uehara, Gavin J Martin, Adam J Bewick, Megan Behringer, Humberto J Debat, Isaac Wong, John C Day, Anton Suvorov, Christian J Silva, Kathrin F Stanger-Hall, David W Hall, Robert J. Schmitz, David R Nelson, Sara Lewis, Shuji Shigenobu, Seth M Bybee, Amanda M Larracuente, Yuichi Oba, Jing-Ke Weng

The Aquilegia genome: adaptive radiation and an extraordinarily polymorphic chromosome with a unique history. Daniele Filiault, Evangeline Ballerini, Terezie Mandakova, Gokce Akoz, Nathan Derieg, Jeremy Schmutz, Jerry Jenkins, Jane Grimwood, Shengqiang Shu, Richard Hayes, Uffe Hellsten, Kerrie Barry, Juyiang Yan, Sirma Mihaltcheva, Miroslava Karafiatova, Viktoria Nizhynska, Martin Lysak, Scott Hodges, Magnus Nordborg

The genome of the water strider Gerris buenoi reveals expansions of gene repertoires associated with adaptations to life on the water. David Armisen, Rajendhran Rajakumar, Markus Friedrich, Joshua B Benoit, Hugh M Robertson, Kristen A Panfilio, Seung-Joon Ahn, Monica F Poelchau, Hsu Chao, Huyen Dinh, HarshaVardhan Doddapaneni, Shannon Dugan-Perez, Richard A Gibbs, Daniel ST Hughes, Yi Han, Sandra L Lee, Shwetha C Murali, Donna M Muzny, Jiaxin Qu, Kim C Worley, Monica Munoz-Torres, Ehab Abouheif, Francois Bonneton, Travis Chen, Li-Mei Chiang, Christopher P. Childers, Andrew G Cridge, Antonin JJ Crumiere, Amelie Decaras, Elise M Didion, Elizabeth Duncan, Elena N Elpidina, Marie-Julie Fave, Cedric Finet, Chris GC Jacobs, Alys Jarvela, Emily J Jennings, Jeffery W Jones, Maryna P Lesoway, Mackenzie Lovegrove, Alexander Martynov, Brenda Oppert, Angelica Lilico-Ouachour, Arjuna Rajakumar, Peter N Refki, Andrew J Rosendale, Maria Emilia Santos, William Toubiana, Maurijn van der Zee, Iris M Vargas Jentzsch, Aidamalia Vargas Lowman, Severine Viala, Stephen Richards, Abderrahman Khila

Cell biology

F-actin patches nucleated on chromosomes coordinate capture by microtubules in oocyte meiosis. Mariia Burdyniuk, Andrea Callegari, Masashi Mori, Francois Nedelec, Peter Lenart

Rab-mediated trafficking in the secondary cells of Drosophila male accessory glands and its role in fecundity. Elodie Prince, Marko Brankatschk, Benjamin Kroeger, Clive Wilson, Dragan Gligorov, Suzanne Eaton, Francois Karch, Robert K Maeda

Persistent cell motility requires transcriptional feedback of cytoskeletal – focal adhesion equilibrium by YAP/TAZ. Devon E Mason, James H Dawahare, Trung Dung Nguyen, Yang Lin, Sherry L. Voytik-Harbin, Pinar Zorlutuna, Mervin E Yoder, Joel D Boerckel

Absence of the Spindle Assembly Checkpoint restores mitotic fidelity upon loss of sister chromatid cohesion. Rui D Silva, Mihailo Mirkovic, Leonardo G Guilgur, Om S. Rathore, Rui Gonçalo Martinho, Raquel A Oliveira

Focal adhesion kinase regulates early steps of myofibrillogenesis in cardiomyocytes. Nilay Taneja, Abigail C Neininger, Matthew R Bersi, W David Merryman, Dylan T Burnette

Recruitment of Two Dyneins to an mRNA-Dependent Bicaudal D Transport Complex. Thomas E. Sladewski, Neil Billington, M. Yusuf Ali, Carol S. Bookwalter, Hailong Lu, Elena B. Krementsova, Trina A. Schroer, Kathleen M. Trybus

RNA-directed activation of cytoplasmic dynein-1 in reconstituted transport RNPs. Mark A McClintock, Carly I Dix, Christopher M Johnson, Stephen H McLaughlin, Rory J Maizels, Ha Thi Hoang, Simon L Bullock

Dynein-2 intermediate chains play crucial but distinct roles in primary cilia formation and function. Laura Vuolo, Nicola L Stevenson, Kate Heesom, David J Stephens

Regulator of calcineurin-2 is a centriolar protein with a role in cilia length control. Nicola Stevenson, Dylan Bergen, Amadeus Xu, Emily Wyatt, Freya Henry, Janine McCaughey, Laura Vuolo, Chrissy Hammond, David Stephens

Actin and Src-family kinases regulate nuclear YAP1 and its export. Nil Ege, Anna M Dowbaj, Ming Jiang, Michael Howell, Robert P Jenkins, Erik Sahai

Rotational 3D mechanogenomic Turing patterns of human colon Caco-2 cells during differentiation. Gen Zheng, Alexandr A. Kalinin, Ivo D. Dinov, Walter Meixner, Shengtao Zhu, John W. Wile

Collagen stiffness modulates MDA-MB231 cell metabolism through adhesion-mediated contractility. Emma J. Mah, Gabrielle E. McGahey, Albert F. Yee, Michelle A. Digman

Tunable molecular tension sensors reveal extension-based control of vinculin loading. Andrew S LaCroix, Andrew D Lynch, Matthew E Berginski, Brenton D Hoffman

CLIC4 is regulated by RhoA-mDia2 signaling through Profilin-1 binding to modulate filopodia length. Elisabetta Argenzio, Katarzyna M Kedziora, Leila Nahidiazar, Tadamoto Isogai, Anastassis Perrakis, Kees Jalink, Wouter H Moolenaar, Metello Innocenti

Shugoshin is essential for meiotic prophase checkpoints in C. elegans. Tisha Bohr, Christian R. Nelson, Stefani Giacopazzi, Piero Lamelza, Needhi Bhalla

Shugoshin protects centromere pairing and promotes segregation of non-exchange partner chromosomes in meiosis. Luciana Previato, Emily L Kurdzo, Craig A Eyster, Mara N Gladstone, Hoa H Chuong, Elena Llano, Alberto M Pendas, Roberto J Pezza, Dean S Dawson

A positive feedback-based mechanism for constriction rate acceleration during cytokinesis in C. elegans. Renat Khaliullin, Rebecca Green, Linda Shi, Michael Berns, J. Sebastian Gomez-Cavazos, Arshad Desai, Karen Oegema

Cell-matrix adhesion controls Golgi organization and function by regulating Arf1 activation in anchorage-dependent cells. Vibha Singh, Chaitanya Erady, Nagaraj Balasubramanian

Modelling

Spatial dynamics of flower organ formation. Yuriria Cortes Poza, Pablo Padilla Longoria, Elena Alvarez Buylla

Mathematical modelling of cortical neurogenesis reveals that the founder population does not necessarily scale with neuronal output. Noemi Picco, Fernando Garcia-Moreno, Thomas Woolley, Philip Maini, Zoltan Molnar

From jamming to collective cell migration through a boundary induced transition. Oleksandr Chepizhko, Maria Chiara Lionetti, Chiara Malinverno, Giorgio Scita, Stefano Zapperi, Caterina A. M. La Porta

Stochastic simulation of pattern formation in growing tissue: a multilevel approach. Stefan Engblom

Self-organization principles of intracellular pattern formation. Jacob Halatek, Fridtjof Brauns, Erwin Frey

Modeling cell-substrate de-adhesion dynamics under fluid shear. Renu Maan, Gautam I Menon, Pramod A Pullarkat

Theory of Morphogenesis. Andrey Minarsky, Nadya Morozova, Robert Penner, Christophe Soule

A mathematical model of the metabolism of a cell. Self-organization and chaos. V.I. Grytsay, I.V. Musatenko

Transition State Characteristics During Cell Differentiation. Rowan Brackston, Eszter Lakatos, Michael P.H. Stumpf

Riding the Cell Jamming Boundary: Geometry, Topology, and Phase of Human Corneal Endothelium. Nigel H Brookes

Stochasticity of cellular growth: sources, propagation and consequences. Philipp Thomas, Guillaume Terradot, Vincent Danos, Andrea Weisse

Statistical Inference in Cell Lineage Trees. Damien G Hicks, Terence P Speed, Mohammed Yassin, Sarah M Russell

Generative adversarial networks uncover epidermal regulators and predict single cell perturbations. Arsham Ghahramani, Fiona M Watt, Nicholas M Luscombe

Information Isometry Technique Reveals Organizational Features in Developmental Cell Lineages. Bradly John Alicea, Thomas E. Portegys, Richard Gordon

In silico mechanobiochemical modeling of morphogenesis in cell monolayers. Bahador Marzban, Xiao Ma, Xiaoliang Qing, Hongyan Yuan

Noise-driven Cell Differentiation and the Emergence of Organization. Hadiseh Safdari, Ata Kalirad, Cristian Picioreanu, Rouzbeh Tusserkani, Bahram Goliaei, Mehdi Sadeghi

Tools & resources

| Imaging etc.

Long-term live imaging of the Drosophila adult midgut reveals real-time dynamics of cell division, differentiation, and loss. Judy Martin, Erin Nicole Sanders, Paola Moreno-Roman, Shruthi Balachandra, XinXin Du, Leslie Ann Jaramillo Koyama, Lucy Erin O’Brien

Application of the Mesolens for sub-cellular resolution imaging of intact larval and whole adult Drosophila. Gail McConnell, William B. Amos

Brain Development: Machine Learning Analysis Of Individual Stem Cells In Live 3D Tissue. Martin Hailstone, Lu Yang, Dominic Waithe, Tamsin J. Samuels, Yoav Arava, Tomasz Dobrzycki, Richard M. Parton, Ilan Davis

Multidirectional digital scanned light-sheet microscopy enables uniform fluorescence excitation and contrast-enhanced imaging. Adam K Glaser, Ye Chen, Chengbo Yin, Linpeng Wei, Lindsey Barner, Nicholas Reder, Jonathan Liu

Forget Pixels: Adaptive Particle Representation of Fluorescence Microscopy Images. Bevan L. Cheeseman, Ulrik Günther, Mateusz Susik, Krzysztof Gonciarz, Ivo F. Sbalzarini

Image-based methods for phenotyping growth dynamics and fitness in Arabidopsis thaliana. Francois Vasseur, George Wang, Justine Bresson, Rebecca Schwab, Detlef Weigel

Mid-infrared optoacoustic microscopy with label-free chemical contrast in living cells and tissues. Miguel A. Pleitez, Asrar Ali Khan, Josefine Reber, Andriy Chmyrov, Markus Seeger, Marcel Scheideler, Stephan Herzig, Vasilis Ntziachristos

High Numerical Aperture Epi-illumination Selective Plane Illumination Microscopy. Bin Yang, Yina Wang, Siyu Feng, Veronica Pessino, Nico Stuurman, Bo Huang

Imaging the Developing Heart: Synchronized Timelapse Microscopy During Developmental Changes. Carl J. Nelson, Charlotte Buckley, John J. Mullins, Martin A. Denvir, Jonathan Taylor

4D blood flow mapping using SPIM-microPIV in the developing zebrafish heart. Vytautas Zickus, Jonathan M. Taylor

Quantitative mapping of fluorescently tagged cellular proteins using FCS-calibrated four dimensional imaging. Antonio Z Politi, Yin Cai, Nike Walther, M. Julius Hossain, Birgit Koch, Malte Wachsmuth, Jan Ellenberg

ChromoTrace: Reconstruction of 3D Chromosome Configurations by Super-Resolution Microscopy. Carl Barton, Sandro Morganella, Oeyvind Oedegaard, Stephanie Alexander, Jonas Ries, Tomas Fitzgerald, Jan Ellenberg, Ewan Birney

Estimating numbers of fluorescent molecules in single cells by analysing fluctuations in photobleaching. Elco Bakker, Peter S. Swain

Using Deep Learning for Segmentation and Counting within Microscopy Data. Carlos X. Hernández, Mohammad M. Sultan, Vijay S. Pande

High-quality ultrastructural preservation using cryofixation for 3D electron microscopy of genetically labeled tissues. Tin Ki Tsang, Eric A Bushong, Daniela Boassa, Junru Hu, Benedetto Romoli, Sebastien Phan, Davide Dulcis, Chih-Ying Su, Mark H Ellisman

| Genome tools

In vivo CRISPR-Cas gene editing with no detectable genome-wide off-target mutations. Pinar Akcakaya, Maggie L. Bobbin, Jimmy A. Guo, Jose Malagon Lopez, M. Kendell Clement, Sara P. Garcia, Mick D. Fellows, Michelle J. Porritt, Mike A. Firth, Alba Carreras, Tania Baccega, Frank Seeliger, Mikael Bjursell, Shengdar Q. Tsai, Nhu T. Nguyen, Roberto Nitsch, Lorenz Mayr, Luca Pinello, Mohammad Bohlooly-Y, Martin J. Aryee, Marcello Maresca, J. Keith Joung

No unexpected CRISPR-Cas9 off-target activity revealed by trio sequencing of gene-edited mice. Vivek Iyer, Katharina Boroviak, Mark Thomas, Brendan Doe, Edward Ryder, David Adams

On the design of CRISPR-based single cell molecular screens. Andrew J Hill, José L McFaline-Figueroa, Lea M Starita, Molly J Gasperini, Kenneth A Matreyek, Jonathan Packer, Dana Jackson, Jay Shendure, Cole Trapnell

Highly efficient CRISPR/Cas9-mediated tissue specific mutagenesis in Drosophila. Amy R Poe, Bei Wang, Maria L Sapar, Hui Ji, Kailyn Li, Tireniolu Onabajo, Rushaniya Fazliyeva, Mary Gibbs, Yue Qiu, Yuzhao Hu, Chun Han

Heterochromatin delays CRISPR-Cas9 mutagenesis but does not influence repair outcome. Eirini M Kallimasioti-Pazi, Keerthi Thelakkad Chathoth, Gillian C Taylor, Alison Meynert, Tracy Ballinger, Martijn J Kelder, Sebastien Lalevee, Ildem Sanli, Robert Feil, Andrew J Wood

Machine learning of stem cell identities from single-cell expression data via regulatory network archetypes. Patrick S. Stumpf, Ben D. MacArthur

Rapid low-cost assembly of the Drosophila melanogaster reference genome using low-coverage, long-read sequencing. Edwin A. Solares, Mahul Chakraborty, Danny E. Miller, Shannon Kalsow, Kate E. Hall, Anoja G. Perera, J.J. Emerson, R. Scott Hawley

High-quality genome assemblies of 15 Drosophila species generated using Nanopore sequencing. Danny E. Miller, Cynthia Staber, Julia Zeitlinger, R. Scott Hawley

Multiple laboratory mouse reference genomes define strain specific haplotypes and novel functional loci. Jingtao Lilue, Anthony G Doran, Ian T Fiddes, Monica Abrudan, Joel Armstrong, Ruth Bennett, William Chow, Joanna Collins, Anne Czechanski, Petr Danecek, Mark Diekhans, Dirk-Dominic Dolle, Matt Dunn, Richard Durbin, Dent Earl, Anne Ferguson-Smith, Paul Flicek, Jonathan Flint, Adam Frankish, Beiyuan Fu, Mark Gerstein, James Gilbert, Leo Goodstadt, Jennifer Harrow, Kerstin Howe, Mikhail Kolmogorov, Stefanie Koenig, Chris Lelliott, Jane Loveland, Richard Mott, Paul Muir, Fabio Navarro, Duncan Odom, Naomi Park, Sarah Pelan, Son K Phan, Michael Quail, Laura Reinholdt, Lars Romoth, Lesley Shirley, Cristina Sisu, Marcela Sjoberg-Herrera, Mario Stanke, Charles Steward, Mark Thomas, Glen Threadgold, David Thybert, James Torrance, Kim Wong, Jonathan Wood, Fengtang Yang, David J Adams, Benedict Paten, Thomas M Keane

Programmable single and multiplex base-editing in Bombyx mori using RNA-guided cytidine deaminases. Qingyou Xia, Yufeng Li, Sanyuan Ma, Le Sun, Tong Zhang, Jiasong Chang, Wei Lu, Xiaoxu Chen, Yue Liu, Xiaogang Wang, Run Shi, Ping Zhao

A modular dCas9-SunTag DNMT3A epigenome editing system overcomes pervasive off-target activity of direct fusion dCas9-DNMT3A constructs. Christian Pflueger, Dennis Tan, Tessa Swain, Trung Viet Nguyen, Jahnvi Pflueger, Christian Nefzger, Jose M Polo, Ethan Ford, Ryan Lister

Addressing the looming identity crisis in single cell RNA-seq. Megan Crow, Anirban Paul, Sara Ballouz, Z. Josh Huang, Jesse Gillis

Enhancing resolution of natural methylome reprogramming behavior in plants. Robersy Sanchez, Xiaodong Yang, Hardik Kundariya, Jose Raul Barreras, Yashitola Wamboldt, Sally Mackenzie

Verified the effectiveness of AsCpf1 system in a variety of vertebrate species. Zhuo Li, Zhaoying Shi, Nana Fan, Yongqiang Chen, Jing Guo, Jingchun Wu, Hong Song, Shilong Chu, Kunlun Mo, Bentian Zhao, Zhen Ouyang, Dandan Tian, Shaoyang Zhao, Jieying Zhu, Jiekai Chen, Yonglong Chen, Liangxue Lai, Duanqing Pei

CRISPR-DT: designing gRNAs for the CRISPR-Cpf1 system with improved target efficiency and specificity. Houxiang Zhu, Chun Liang

CONSTRUCTION OF WHOLE GENOMES FROM SCAFFOLDS USING SINGLE CELL STRAND-SEQ DATA. Mark Hills, Ester Falconer, Kieran O’Neil, Ashley Sanders, Kerstin Howe, Victor Guryev, Peter M Lansdorp

Cas-CLIP: a method for customizing pooled CRISPR libraries. Jiyeon Kweon, Da-eun Kim, An-Hee Jang, Yongsub Kim

TOGGLe, a flexible framework for easily building complex workflows and performing robust large-scale NGS analyses. Christine Tranchant-Dubreuil, Sebastien Ravel, Cecile Monat, Gautier Sarah, Abdoulaye Diallo, Laura Helou, Alexis Dereeper, Ndomassi Tando, Julie Orjuela-Bouniol, Francois Sabot

An Interpretable Framework for Clustering Single-Cell RNA-Seq Datasets. Jesse M Zhang, Jue Fan, H. Christina Fan, David Rosenfeld, David N. Tse

Research practice & education

Gender balance in time-keeping at life science conferences. Petra Edlund, Erin M Tranfield, Vera van Noort, Karen Siu Ting, Sofia Tapani, Johanna Hoog

Building a local community of practice in scientific programming for Life Scientists. Sarah L.R. Stevens, Mateusz Kuzak, Carlos Martinez, Aurelia Moser, Petra M. Bleeker, Marc Galland

The impact on authors and editors of introducing Data Availability Statements at Nature journals. Rebecca Grant, Iain Hrynaszkiewicz

Intellectual Synthesis in Mentorship Determines Success in Academic Careers. Jean F Lienard, Titipat Achakulwisut, Daniel E Acuna, Stephen V David

Reproducible big data science: A case study in continuous FAIRness. Ravi K Madduri, Kyle Chard, Mike D’Arcy, Segun C Jung, Alexis Rodriguez, Dinanath Sulakhe, Eric W Deutsch, Cory Funk, Ben Heavner, Matthew Richards, Paul Shannon, Ivo Dinov, Gustavo Glusman, Nathan Price, John D Van Horn, Carl Kesselman, Arthur W Toga, Ian Foster

Twenty steps towards an adequate inferential interpretation of p-values. Norbert Hirschauer​, Sven Grüner​, Oliver Mußhoff, Claudia Becker

Sci-Hub provides access to nearly all scholarly literature. Daniel S Himmelstein, Ariel R Romero, Jacob G Levernier, Thomas A Munro, Stephen R McLaughlin, Bastian Greshake Tzovaras, Casey S Greene

Sharing is not erring: Pseudo-reciprocity in collective search. Imen Bouhlel, eCharley M. Wu, Nobuyuki Hanaki, Robert L. Goldstone

Why not…

FGF21, a liver hormone that inhibits alcohol intake in mice, increases in human circulation after acute alcohol ingestion and sustained binge drinking at Oktoberfest. Susanna Soeberg, Emilie S. Andersen, Niels B. Dalgaard, Ida Jarlhelt, Nina L. Hansen, Nina Hoffmann, Tina Vilsboell, Anne Chenchar, Michal Jensen, Trisha J. Grevengoed, Sam A.J. Trammell, Filip K. Knop, Matthew P. Gillum

Biomechanics of the peafowl’s crest: a potential mechanosensory role for feathers during social display. Suzanne Amador Kane, Daniel Van Beveren, Roslyn Dakin

(No Ratings Yet)

Loading...