As developmental biologists, we are fascinated by the ability of an organism to become, from a single fertilised egg, a fully functional individual. However, as human beings we are equally curious about how the Homo sapiens species arose and became different to all other animals on the planet. As a group of students from the Centre for Developmental Neurobiology at King’s College London we won the opportunity to explore this issue in depth as guest commissioners and editors for The Biochemist magazine.
In this special issue, published this month, arguably the place to start was in the oceans around 3.5 billion years ago: Nick Lane, the author of bestselling science books including “Life Ascending” and “Power, sex, suicide” explored how the first living cells formed multicellular organisms and why energy is the driving force of evolution.
Of course, we wouldn’t be who we are without our brains! Learn about how the first neuronal proteins and structures evolved 500 million years ago from Dwayne Godwin and Melissa Masicampo in our second article.
Continuing in the exploration of the nervous system, Maria Martínez-Martínez and Víctor Borrell look at the size of the cortex as the core of human uniqueness.
The brain is not, however, the only thing that makes us different to other animals. The way we digest food, especially lactose, is also uniquely important for understanding our evolutionary history. Read the wonderful article by Dallas Swallow to find out more about how our ability to digest milk has made us who we are today.
All the information we possess about our evolutionary history and the genes that make us human awaits a tremendous boost of detailed new data that can be gathered from the now available genomic databases. Rebecca Lowdon and Devjanee Swain-Lenz look at the ENCODE project and assess how it can help us understand our past, but also allow us to shape our own future as a species.
To put it all in context, read a succinct introductionwritten by members of our team: Rebecca McIntosh and Danielle Stevenson with a handy timeline drawn by Tristan Varela.
We have had great fun commissioning the articles and thank all our contributors. We are confident you will find the issue stimulating and fascinating and hope that it will help you on your own quest to understand what has made you human.
Tenure track positions as Assistant Professor within the Wallenberg Centre for Molecular Medicine at Umeå University, Sweden.
Deadline 1st of December 2015
The Wallenberg Centre for Molecular Medicine (WCMM) at Umeå University, Sweden, has been established as part of a national agenda with the goal of regaining a leading position for Sweden within medical research. The Centre is a collaboration between Knut and Alice Wallenberg’s Foundation, Umeå University, Västerbotten County Council, the Kempe Foundations and the Cancer Foundation for Northern Sweden. In this call, the Centre is looking for up to four outstanding researchers, to be positioned within one or more of the following areas of molecular medicine: cancer, infection biology, metabolism/diabetes or neuroscience. The positions are provided with a generous support package including funding for Postdoctoral Associates and PhD Student recruitments. The successful candidates will be working in strong internationally recognized research environments and have access to excellent local and national research infrastructures including unique collections of longitudinal samples in existing biobanks.
Work description The successful candidates will be working in close in close proximity to established research groups within one or more of the focus areas of cancer, infection biology, metabolic disorders including diabetes or neuroscience. The candidates are expected to initiate and maintain a strong research program complementing on-going research within molecular medicine at Umeå University, Sweden, and to take active part in collaborative research opportunities and exchange programs within the new network of WCMM centres at other universities in Sweden.
The successful candidates will primarily be conducting research. Up to 20% of the employment can be devoted to teaching so that the criteria for promotion to a tenure position as Senior Lecturer/Associate Professor (Universitetslektor) can be fulfilled within four years.
Qualifications To be eligible for the positions, candidates must have a PhD degree, completed no more than seven years prior to the deadline for application. A candidate who has completed their degree prior to this time could be given equal priority if special circumstances exist. Special circumstances include absence due to illness, parental leave or clinical employment, appointment of trust in trade union organizations or similar circumstances. We are seeking outstanding candidates with documented excellent research in fields relevant to molecular medicine. The candidate must have appropriate postdoctoral training outside the university at which the PhD was defended.
More about the position The position will be provided with a generous support package including funding for Postdoctoral Associates and PhD Students as well as substantial support for running costs. To qualify for promotion, the candidates are expected to complement the funding with their own national and/or international grants. The researcher will work within one or more of the 13 departments of the Faculty of Medicine. The Department in which the candidate formally will be employed will be decided in consultation between the applicant and the faculty. An individual scientific and educational development plan will be formulated upon agreement between the applicant and the Head of Department at which the applicant will be employed. One pedagogical and two scientific mentors will be appointed to support the career of the candidate.
YOU FIND MORE INFORMATION ABOUT THE POSITIONS AND HOW TO APPLY:
Originally posted to the blog Genes to Genomes, reposed with permission.
Don Gibson (University of California, Davis) describes how he decided to start the Barbara on the Bill Campaign
When I heard that the U.S. Department of the Treasury announced that a woman will be on the $10 bill, I started reading several articles about which woman it should be. I was shocked that so few women of science were being mentioned. I thought we, as scientists, should fix this. One woman kept coming to mind. This woman revolutionized genetics & biology, suffered harsh discrimination during her career, and remains the only woman to single-handedly win a Nobel Prize in life science: Barbara McClintock.
This idea started back in February when I saw Neil deGrasse Tyson give a public talk. He showed currency from nations around world. Many countries had their great scientists and discoveries on their coins and paper bills. While America’s money had only one theme: old, white, male politicians. He inspired me to think about national values, and there is no place more prominent for a national value then a nation’s currency.
America may be the leader in science today, but if it does not value science, other nations may surpass this country in the future. Having a woman of science on our currency could be a turning point in the way Americans view science. It could also highlight the success of real scientists who face injustice. McClintock was held back from permanent positions multiple times in her career because of her gender. She was able to succeed despite these set-backs through hard work, eventually designing ground-breaking genetics experiments in a lab of her own. Even today, challenges as a result of gender discrimination still exist; only one in four jobs in STEM is held by a woman.
Surprisingly, when I asked fellow graduate students in science fields to name a historical American woman scientist, they were often at a loss.
“I was shocked when I realized I couldn’t name any other female American scientists from history, ” said fellow geneticist Anastasia Bodnar, Policy Director at Biology Fortified, a science education and advocacy non-profit organization.
Several of my mentors are amazing women scientists. I am a firm believer that they need to be more recognized for their contributions to science. McClintock’s contributions were prolific and I see advocating for her to be on the $10 bill as a great way to give back to the female mentors I have had.
I know that a number of scientists, including McClintock, do not seek fame. Many other great women are also being advocated for the $10 bill, but as scientists we need to advocate for ourselves in public spaces for our contributions to be widely recognized. Whether or not Barbara McClintock is selected, I consider this effort a success, if this project increases the dialogue surrounding women in science.
The campaign is seeking public support though barbaraonthebill.com, and the Department of the Treasure is taking public feedback. You can also comment via Facebook and Twitter using the hashtag #TheNew10.
Zebrafish is a common model organism in many fields of science. The study by Sundvik et al. 2015 in Scientific Reports tests the safety of acoustic levitation of an intact organism using zebrafish embryos (Figure 1). Acoustic levitation has over the last few decades been developed to provide a wall- and contactless environment to transfer and manipulate small objects, more recently cells and even entire organisms. This method has great potential that could be useful also outside physics labs. A zebrafish in a levitator encounters sound levels comparable to those next to a screaming jet engine, but the sound is still inaudible to humans. From a developmental point of view it is interesting to note that the developing zebrafish are insensitive to the harsh conditions in the levitator. The fish develops normally in the apparently gravitation-free space, in the node of the sound waves, when sonified for a short time between one and 12 hours after fertilization. It is unknown whether levitation at even later time points after fertilization affects the fish development. We found that fish do die if the water surrounding the embryo evaporates. A controllable microclimate around the levitator could permit investigating whether longer levitation periods affect the development and patterning of tissues and organs in the levitated fish. Such a setup would permit levitating the zebrafish for days, potentially without liquid immersion for some developmental stages. This study is a beginning and only imagination restricts the possibilities of this approach.
Figure 1. A levitating zebrafish embryo inside an ellipsoidal water droplet. Photography: Mr Eetu Lampsijärvi
Dimitri Perrin3, Shimpei I. Kubota1,2, Kazuki Tainaka1,2 & Hiroki R. Ueda1,2,4*
1Department of Systems Pharmacology, The University of Tokyo, Tokyo, Japan.
2CREST, Japan Science and Technology Agency, Saitama, Japan.
3School of Electrical Engineering and Computer Science, Science and Engineering Faculty, Queensland University of Technology, Brisbane, Australia.
4Laboratory for Synthetic Biology, RIKEN Quantitative Biology Center, Osaka, Japan.
Correspondence should be addressed to H.R.U. (uedah-tky@umin.ac.jp, Tel: +81-3-5841-3415, Fax: +81-3-5841-3418)
Fig.1: Thy1-YFP-H Tg brain, cleared with CUBIC reagents and imaged using Macrozoom Light-sheet Fluorescence Microscopy
The brain is an organ like no other, in part because of its function. It has been recognised as the location of imagination, memory, thought and sensation since Claudius Galenus, but details about its structure only start to emerge in the late 17th century. Thomas Willis proposes the concept of a regionalisation of brain activities and Antonie van Leeuwenhoek’s work on microscopy reveals that nerves are not hollow conduits for ‘animal spirits’.
While further advances (such as Luigi Galvani on the role of electricity in the nervous system) move 18th century scientists closer to understanding the brain, the mystic surrounding the organ remains after Matthias Jakob Schleiden and Theodor Schwann propose their cell theory. All organs follow the three tenets that all living organisms are composed of one or more cells, the cell is the most basic unit of life, and all cells arise from pre-existing, living cells. All organs, except the brain. Dyes used to reveal the cellular structures of tissues only show a dense and entangled network of fibres. No cells are visible in the brain.
Fifty years later, Santiago Ramón y Cajal starts using Camillo Golgi’s reazione nera, which has the distinct advantage of staining a limited number of cells at random and in their entirety. Fine details can, finally, be observed. Ramón y Cajal pushes forward the idea of a modular brain and cells as emitter/receptor. By viewing less, the method allows to see more.
While EEG, implants and fMRI now allow measurements of group cells or indirect observation of overall activity patterns, light diffraction due to lipids means that brains cannot be directly imaged. Slicing is still used, and requires time-consuming and error-prone computational reconstruction of the whole organ.
Tissue clearing, by contrast, removes these lipids and finally allows high-resolution whole-brain imaging, therefore preserving important structures. It is a crucial step, and it is fitting that Karl Deisseroth and his team show a transparent brain sitting over a Ramón y Cajal quote in their 2013 article on CLARITY. By viewing less, we can see more, but seeing is only the beginning.
Learning, memory, behaviour and all other cognitive functions emerge from structure and cell-to-cell interactions, making understanding cellular circuits in the brain essential to advances in Neuroscience. Coupled with key technologies such CRISPR/Cas-mediated genetic engineering, tissue clearing has the potential to have for this field the impact that microarrays had on Genetics.
This requires two properties: (i) tissue clearing must be safe, rapid, efficient and easily reproducible, (ii) computational tools must be developed to analyse these new high-resolution 3D images. Our method, CUBIC, has been developed to address these needs.
Fig.2: Overview of the CUBIC protocol, reproduced from our recent Nature Protocols article [4]
Our new aminoalcohol-based clearing cocktails have no safety concerns and preserve signals from fluorescence proteins. Whole-brain clearing can be achieved by immersing a whole brain in CUBIC reagents for two weeks. In our 2014 Cell article, we showed this protocol is also applicable to a marmoset brain, which is a model animal closer to the human.
For the biologist end-user, imaging the cleared sample is a largely automated process. Our vision is to make the analysis as straightforward, with information about the experimental setup enough to identify the anatomical brain regions where changes in expression occur (and estimate the statistical significance of these changes). We have already developed tools for these analysis steps, with an initial pipeline described in our recent Nature Protocols article and available for download, and we are now working on improving the registration steps and the detection of active cells.
We have also shown that tissue clearing is useful not only for the brain but also for other organs and for whole-body imaging. Because we noticed aminoalcohols in the CUBIC reagent could decolourise the endogenous pigments such as heme, we developed a direct transcardial perfusion of the CUBIC reagent for further transparency. This perfusion protocol enables whole-body or whole-organ clearing within 10 days to 2 weeks.
Our new protocol provides access to a new world. CUBIC makes it possible to visualise and quantify a targeted small minority cells in the 30 billion cells of a mouse body. This is helpful to understand cellular mechanisms of autoimmune disease and cancer micrometastasis. Of course, our new protocol is not limited to model organisms expressing fluorescent proteins. CUBIC is compatible with immunohistochemistry so we can apply our method to human pathology, for which fluorescence imaging is not possible.
Further reading:
K. Chung, J. Wallace, S.-Y. Kim, S. Kalyanasundaram, A. S. Andalman, T. J. Davidson, J. J. Mirzabekov, K. A. Zalocusky, J. Mattis, A. K. Denisin, S. Pak, H. Bernstein, C. Ramakrishnan, L. Grosenick, V. Gradinaru and K. Deisseroth (2013). Structural and molecular interrogation of intact biological systems. Nature 497, 332–337. DOI: http://dx.doi.org/10.1038/nature12107
E. A. Susaki, K. Tainaka, D. Perrin, F. Kishino, T. Tawara, T. M. Watanabe, C. Yokoyama, H. Onoe, M. Eguchi, S. Yamaguchi, T. Abe, H. Kiyonari, Y. Shimizu, A. Miyawaki, H. Yokota and H. R. Ueda (2014). Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis. Cell 157, 726–739. DOI: http://dx.doi.org/10.1016/j.cell.2014.03.042
K. Tainaka, S. I. Kubota, T. Q. Suyama, E. A. Susaki, D. Perrin, M. Ukai-Tadenuma, H. Ukai and H. R. Ueda (2014). Whole-body imaging with single-cell resolution by tissue decolorization. Cell 159, 911–924. DOI: http://dx.doi.org/10.1016/j.cell.2014.10.034
E. A. Susaki, K. Tainaka, D. Perrin, H. Yukinaga, A. Kuno and H. R. Ueda (2015). Advanced CUBIC protocols for whole-brain and whole-body clearing and imaging with single-cell resolution. Nature Protocols 10, 1709–1727. DOI: http://dx.doi.org/10.1038/nprot.2015.085
In autumn, crickets generally exhibit chirping songs in the temperate East Asian country of Japan. While the African field cricket Gryllus bimaculatus originates from tropical countries, it is an emerging model animal globally because of its ability to regenerate amputated legs during nymph and its developmental mode (short germ band) (Mito and Noji, 2008).
Many living organisms in the animal kingdom are able to regrow their body parts following injury. Examples of body parts that may be regrown include the lens and tail of amphibians, the head of planarians, and the heart of fish. In contrast, it has long been assumed that humans cannot restore lost body parts, except for particular tissues, including the epidermis, the liver, and the ovarian surface after ovulation. Therefore, it is important to elucidate the molecular mechanisms involved in regeneration processes using animal models that are able to regenerate body parts for subsequent application in non-regenerative human organs and tissues.
Within the last 2 years, comparative genomic studies of two planarian species with different regenerative abilities led to the successful regeneration of heads by reducing beta-catenin activity from otherwise non-regenerative tail fragments (Umesono et al., 2013). Studies of vertebrates with the ability to restore limbs, including newts, frogs, and salamanders, have demonstrated that limb regeneration occurs in a stepwise manner. The limb regeneration process is divided into at least three phases: wound healing, dedifferentiation, and redevelopment, with the redevelopment phase mimicking embryonic development (Endo et al., 2004).
The cricket leg is composed of six segments that are arranged along the proximo-distal (PD) axis: coxa, trochanter, femur, tibia, tarsus, and claw (Figure 1). The tarsus is further subdivided into three tarsomeres. When the tibia of the third-instar nymph is amputated, the leg regenerates and recovers its allometric size and proper shape by the sixth instar (i.e., within 20 days of amputation), being restored to almost normal adult size and shape. Soon after healing, the blastema (a pool of cells that proliferate) develops in the distal region of the amputated leg. Blastema cells proliferate and form the missing structures by intercalary processes between the most distal region and the remaining part of the leg (French et al., 1976).
Previously, we performed comparative transcriptome analysis of regenerating and normal amputated legs of crickets to profile mRNA expression associated with leg regeneration (Bando et al., 2013). We first focused on the upregulation of Jak/Stat pathway genes, which are linked to the immune system. RNA interference (RNAi) of genes in this pathway thoroughly disturbed leg regeneration. In contrast, RNAi against Socs, a suppressor of cytokine signaling, caused leg elongation. Additional experiments showed that the Jak/Stat pathway promotes cell proliferation downstream of the Ds/Fat pathway.
Subsequently, we investigated epigenetic regulation during cricket leg regeneration. Tetsuya Bando, a senior investigator in our group, identified one gene for histone H3 lysine 27 (H3K27) methyltransferase, E(z), and one gene for histone H3K27 demethylase, Utx, in G. bimaculatus. Cloning Gryllus genes is now a straightforward process due to information being available about the cricket genome (Mito and Noji, personal communication). Methylation of histone H3K27 by E(z) represses the expression of target genes by recruiting Polycomb group proteins. Conversely, demethylation of the trimethylated histone H3K27 by Utx promotes gene expression. Tetsuya found that the transcription of both E(z) and Utx genes is upregulated in the blastema cells of amputated legs (Bando et al., 2013). In situ hybridization verified that both genes are ubiquitously transcribed in the regenerating legs of crickets, and that both genes are expressed in developing embryos (Hamada et al., 2015). Immunostaining on the amputated tiny legs after RNAi by Yoshimasa Hamada (a PhD student) confirmed that E(z) and Utx contribute to the methylation and demethylation at histone H3K27me3, respectively, during leg regeneration.
However, Yoshimasa unexpectedly found that the extra leg segment is formed after RNAi against E(z) (Figure 1). Initially, we were not able to determine the identity of the leg segment. Morphologically, the leg segment appeared to be a tibia, because it had spines and spurs that were characteristic to an authentic tibia. Our opening hypothesis was that the phenotypes after RNAi might depend on the amputation site in the tibia. However, even when a leg is amputated in the distal part of the femur, the extra tibia-like segment emerges. Pattern formation along the antero-posterior and dorso-ventral axes remained unchanged, except along the PD axis. We then examined whether the amputation site along the PD axis in the tibia influenced phenotypic severity. The extra-tibia that formed became longer the more proximal the amputation sites on the tibia (Figure 1). Conversely, RNAi against Utx resulted in the loss of joint formation between tarsomere 1 (Ta1) and Ta2 (Figure 2). In situ hybridization showed that the expression of leg patterning genes altered along the PD axis. Specifically, the domain of dachshund (dac) expression expanded in E(z)RNAi regenerating legs, whereas Egfr expression diminished in UtxRNAi legs. Therefore, E(z) may repress dac expression during normal leg regeneration, whereas Utx induces Egfr expression.
dac encodes a transcriptional co-repressor that is categorized in leg gap genes. dac produces crude positional values along the PD axis of the leg and mediates the formation of the distal tibia and Ta1 (the proximal tarsomere) during cricket leg regeneration (dac expression domain is shown in green in Figure 2) (Ishimaru et al., 2015). Specifically, dac promotes tibial cell proliferation. Therefore, because RNAi against E(z) upregulates dac, E(z) expression in the blastema cells may suppress the blastemal overproliferation by repressing extra dac expression.
This information raises the question of how E(z) specifically regulates dac expression. Furthermore, what is the mechanism that determines the target genes of E(z)? E(z) belongs to the Polycomb repressive complex 2 (PRC2), which is one of three Polycomb group (PcG) complexes (Schuettengruber et al., 2007). During cricket embryogenesis, E(z) represses the anterior expansion of Hox gene expression and provides proper identity in embryos (Matsuoka et al., 2015). This information indicates that the target genes of E(z) differ depending on the cellular context. A DNA binding protein, Pleiohomeotic (Pho), along with other factors, binds to the Polycomb response elements (PRE) of target genes, after which E(z) trimethylates histone H3K27. Although PREs have only been identified in Drosophila, the meta-analysis of putative target genes for PcG proteins has shown that many of the target genes are common to the fly, mouse, and humans. dac and Egfr are included among these genes (Schuettengruber et al., 2007). Thus, the regulatory region of the cricket dac gene probably contains PREs, through which E(z) epigenetically regulates the expression of dac during cricket leg regeneration (Figure 2). Ongoing research is focused on characterizing the functions of the Pho gene and other PcG complex genes and epigenetic modifiers during Gryllus leg regeneration.
Finally, why does E(z) RNAi cause extra-tibia formation? One hypothetical scenario is that when the tibia is amputated at the proximal position where dac expression is low, Utx expression (which dominates E(z) expression) permits dac expression (Figure 3a) to restore the tibia. Thus, these histone modifiers sense the positional values along the PD axis of the amputation site, and fine-tune the expression level of leg patterning genes, like dac. In the case of E(z) RNAi just before proximal amputation, intense dac expression is induced and expands in the regenerating leg (Figure 3b). Distal-less (Dll) expression, which is another leg gap gene that specifies the distal domain of the leg (Angelini and Kaufman, 2005), may shift more distally depending on expanded dac expression (Figure 3b). Thus, the Egfr-expressing domain may be separated into two parts where (1) Dll expression is low and (2) Dll is high. The extra-tibia probably forms between the two different Egfr-expressing domains by intercalating cell proliferation and patterning (Figure 3c).
Our goal is to elucidate blueprints for “making a regenerated leg” by using this attractive hemimetabolous insect model. The blueprints are expected to clarify how the number of leg segments is determined. Our striking observations on RNAi against E(z) leading to “extra tibia formation” represent an important step towards elucidating this process.
Journal of Cell Science is pleased to welcome submissions for consideration for an upcoming Special Issue on 3D Cell Biology. We have a limited understanding of cells within their natural context of tissues and organs, but recent advances in imaging techniques, organoids and other more complex systems are making it easier for cell biology research to be conducted in more complex and physiologically relevant settings. Ultimately, we hope to achieve a sophisticated molecular understanding of how cells build organs during development and corrupt their structure and function during disease processes. Journal of Cell Science is a natural home for the research that will help to address these fundamental biological questions.
We invite you to showcase your breakthrough research on all aspects of 3D Cell Biology in this Special Issue, which is scheduled for publication in mid 2016 and will be widely marketed and distributed at relevant conferences worldwide. The articles within this issue will receive extensive exposure to a broad audience of cell biologists.
The issue will be guest edited by Andrew Ewald (Johns Hopkins School of Medicine, USA), who is also the Journal of Cell Science Guest Editor and will handle all 3D cell biology papers submitted to the journal for one year, from August 2015.
We encourage submissions of Research Articles and Short Reports, and Tools & Techniques papers. Articles must be received by January 16th, 2016 for consideration for the Special Issue. Please refer to our author guidelines for information on preparing your manuscript for Journal of Cell Science, and submit your manuscript via our online submission system. Please highlight that your submission is to be considered for the Special Issue in your cover letter. For rapid feedback on the potential suitability of an article for this Special Issue, please submit a presubmission enquiry.
Here is some developmental biology related content from other journals published by The Company of Biologists.
Modelling Alzheimer’s Disease in vitro
Hall and colleagues established an in vitro model of Alzheimer’s Disease by culturing and differentiating embryonic stem cells isolated from the APPsw transgenic minipig. They use this system to provide insights into astrocyte and radial glia pathology in this disease. Read the paper here [OPEN ACCESS].
RhoC regulates VEGF signalling
The small GTPases RhoA and RhoB are involved in vasculogenesis and angiogenesis; however, the role of another Rho family member, RhoC, in these processes is less understood. Now, Mukhopadhyay and colleagues show that RhoC maintains vascular homeostasis in endothelial cells yet is dispensable for vascular development. Read the paper here.
MyoD gets rid of Twist-1 with miR-206
MyoD and Twist-1 are transcription factors known to promote and inhibit muscle cell differentiation respectively. Phylactou and co-workers identify a mechanism of myogenesis in which MyoD and miR-206 downregulate the expression of Twist-1. This pathway might also play an important role in muscle disease. Read the paper here.
PP6 gets oocytes out of meiosis
PP6 is known to modulate Aurora A activity in mitosis, but what is its role in meiosis? Xu, Yang, Su and colleagues present in vivo evidence showing that PP6 suppresses Aurora A activity in oocytes in meiosis II, and is crucial for meiosis II exit, euploid egg production and female fertility. Read the paper here.
The relationship between bone adaptation and mesenchymal stem cells
Wallace and colleagues expose growing mice to exercise, showing that the ability of the progenitor population to differentiate toward bone-forming cells may be a better correlate to bone structural adaptation than external forces generated by exercise. Read the paper here.
A portuguese person, a spanish person and an english person meet in a bar…
… and start discussing developmental biology. This may sound like the beginning of a joke, but in fact happened during the Joint Meeting of the Portuguese, Spanish and British Societies for Developmental Biology, which took place in Algarve, Portugal, in early October. The meeting venue, besides having the aforementioned bar, was also closely located to the beach, which we were able to enjoy thanks to a pleasant weather. Some of the participants also took advantage of the beautiful and family-friendly location to bring their own families. Nevertheless, the scientific talks and poster sessions still managed to draw the participants away from the seaside.
A meeting by the sea. Photo by Catarina Vicente @the_node.
The meeting started with early development, with a plenary lecture on the principles of pluripotency presented by Austin Smith. The lecture focused on the ongoing quest to establish human naïve embryonic stem cells in vitro independently of pluripotency transgenes, showing the progresses achieved so far and presenting the challenges that still need to be overcome.
The transition from pluripotency to lineage commitment was explored by Sally Lowell, whose work identified some of the factors that prime cells for differentiation and revealed a role for adhesion molecules in the decision to differentiate. Berenika Plusa presented the advantages of using rabbit as an alternative model to study early mammalian development. Andrew Johnson showed that axolotl, an organism without extraembryonic tissues, can be used to study later roles of the pluripotency factor Nanog.
The regulation of neuronal differentiation was also the focus of several talks. Kate Storey showed how differentiating neurons in the chick neural tube undergo apical abscission and revealed new evidence for the involvement of microtubule dynamics and adhesion molecules in this process. Also in the chick neural tube, Elisa Marti presented work on the role of Shh signalling in the decision to proliferate or differentiate and showed that the subcellular localisation of several Shh pathway components contributes for this decision. Anna Philpott also talked about division/differentiation in the nervous system and the regulation of proneural factor activity by phosphorylation in Xenopus. François Guillemot highlighted the role of the proneural factor Ascl1 in adult brain neurogenesis and how modulation of Ascl1 stability affects the balance between quiescence and differentiation. The talk by Alexandre Raposo was also on Ascl1 and its function promoting chromatin accessibility during neurogenesis.
The link between adult neural stem cells and cancer was discussed by two drosophilists. Cláudia Barros is using a fly brain tumour model to identify new factors involved in tumour initiation, while Rita Sousa-Nunes is using this model to study the interaction between tumour cells and the microenvironment.
Moving away from neural lineages, we also heard about regulation of proliferation, differentiation and cell movement of presomitic mesoderm progenitors from Leonor Saúde and single cell oscillators as components of the segmentation clock during somitogenesis from Andrew Oates.
Later in development, the formation of the inner ear lumen in zebrafish was introduced by Berta Alsina, revealing that mitotic cell rounding and epithelial thinning regulate lumen expansion. Juan R. Martinez-Morales talked about optic cup morphogenesis in zebrafish, showing that both rim involution and basal constriction contribute to cup folding. Zebrafish embryos were also the stars in the beautiful movies shown by Claudia Linker, whose work combined live imaging with cell ablation to test the role of leader, follower and pre-migratory cells in the collective migration of neural crest cells.
At the chromatin level, Ana Pombo proposed that the priming of developmental genes for future expression in embryonic stem cells involves the Polycomb complex, a specific modification of the RNA polymerase II and local transcript degradation. Rui Martinho showed how chromatin remodelling is involved in the transcriptional reactivation of the Drosophila oocyte during meiosis. Javier Lopez-Rios presented his work on a limb-specific enhancer responsible for the spatial differences in Ptch1 expression between mice and bovine, which underlies their distinct limb anatomy.
The meeting ended with a plenary talk by Moisés Mallo, who presented his work on Gdf11 as the coordinator of the trunk to tail decision during vertebrate embryogenesis and revealed an unexpected role for a pluripotency gene in trunk specification.
The meeting included many other exciting talks that have not been reported here. Overall, the meeting programme showcased the diversity of the developmental biology field in terms of subjects and model systems. The meeting also achieved a perfect gender balance among speakers – 17 female and 17 male speakers. Outside the lecture hall, scientific discussions continued throughout the free afternoons and outdoor poster sessions while enjoying the warm weather. And, of course, in the bar.
As the meeting came to an end, the sunny weather turned into a rainy storm, which made the departure a little less sorrowful.
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MyoD and Twist-1 are transcription factors known to promote and inhibit muscle cell differentiation respectively. Phylactou and co-workers identify a mechanism of myogenesis in which MyoD and miR-206 downregulate the expression of Twist-1. This pathway might also play an important role in muscle disease. Read the paper 
