The results of the latest image competition, this time featuring five beautiful stem cell images, are in! In what rapidly turned into a two horse race between the corn snake dental organ, and the  mouse hippocampus, it was the confocal image of the adult mouse hippocampus that eventually came out on top.

Taken by Lulu Xing of the University of Melbourne and titled “The Garden of Memory”, this striking  image will be appearing on a cover of Development in the coming weeks.

Many thanks to all who submitted an image for this competition – especially those who made the Final Five – and to everyone who voted. You’ve definitely proved that stem cells can be just as visually stunning as the tissues, organs and organisms you’re more used to seeing on the cover of the journal!

(2 votes)

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Monday is tax day for most of us on the American side of the pond.  That ought to cause massive hair loss for many folks, but we have amazing hair follicles that constantly regenerate hair throughout our adult lives (well, at least for those of us without male pattern baldness).  A recent paper in Development helps us understand the hair follicle stem cells involved.

Our hair follicles maintain hair growth throughout our adult lives, and go through different predictable phases of growth (anagen), regression (catagen), and rest (telogen).  Each follicle is a little homeostatic system with adult stem cells that have the ability to self-renew and generate all of the cells required in the hair follicle.  It is not completely understood how all of these mechanisms function together to achieve long-term homeostasis, but a recent paper helps identify the lineage progression of the different cell types in the follicle, and the relationships between them.  Takeda and colleagues identified the marker Hopx in adult hair follicle stem cells.  Lineage-tracing experiments showed that Hopx+ cells give rise to all cell types in the fair follicle.  Takeda and colleagues also identified a novel population of Hopx+ cells in the lower hair bulb of follicles in anagen.  Later in telogen, these newly-identified cells differentiate into the K6+ inner bulge layer in the stem cell niche, where they regulate the quiescence of nearby hair follicle stem cells.  In the image above, Hopx (green) is found in several regions of a hair follicle in anagen.  K6+cells (red) are the innermost cells surrounding the hair follicle shaft.

For a more general description of this image, see my imaging blog within EuroStemCell, the European stem cell portal.

Takeda, N., Jain, R., LeBoeuf, M., Padmanabhan, A., Wang, Q., Li, L., Lu, M., Millar, S., & Epstein, J. (2013). Hopx expression defines a subset of multipotent hair follicle stem cells and a progenitor population primed to give rise to K6+ niche cells Development, 140 (8), 1655-1664 DOI: 10.1242/dev.093005

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In this second part of my BSDB/BSCB spring meeting report, I will attempt to paint a picture of the scientific content of the conference in broad brush strokes. I have grouped talks into overarching topics and will highlight some of my favourites in each category.

Epigenetics

It is only on rare occasions that a presentation makes you go “wow” and forces you to reconsider your thinking about the most fundamental element of our bodies, the cell, and how it works. I experienced one of these moments as I was listening to Mike White (University of Manchester, UK) talk about his work on cell to cell heterogeneity. He presented fascinating live imaging data demonstrating that several molecules of the NFkB pathway periodically change location within the cell at distinct rates. Based on this, he suggested that the position of proteins could be just as important in determining the cellular response to a stimulus as the signal itself. This would add a whole new dimension to consider in the study of cell biology, which seems both exciting and daunting at the same time.

I was also particularly impressed by Martin Howard’s (John Innes Centre, UK) research, which combines experimentation and mathematical modelling to investigate epigenetics in plants. By equating histone modifications with a binary system, his group found that genes can only exist in a state of silenced (“0”) or active (“1”) state. What seems like a smooth transition from one state to the other at an organismal level is in reality caused by a change in the fraction of cells that are “0” or “1”. He also showed preliminary experimental data to support this model. Granted, the main reason I was so awed by this talk was most likely my limited understanding of mathematics, much less mathematical modelling. Regardless, I believe it illustrated the value of using mathematics to formulate elaborate hypotheses which can then be tested and validated through laboratory science.

Other recurring topics throughout the meeting included RNAi and epigenetic reprogramming in early development. Barabara Pernaute (National Institute of Medical Research, UK) presented her work on the role of miRNAs in naive embryonic stem cells compared to epiblast cells in post-implantation embryos. Similarly, Juriaan Holzenspies’ (University of Copenhagen, Denmark) presentation focused on histone marks and RNA polymerase phosphorylation states in blastocyst and epiblast. As part of the post-graduate symposium, Siyao Wang (University of Manchester, UK) presented her PhD research on the role of MLL in germ line cells of the C. elegans embryos and Richard Kaschula (University of Sussex, UK) talked about ubx-targeting miRNAs in Drosophila. Finally, Danesh Moazed (Harvard Medical School, USA) focused on his work into the mechanisms of RNAi-mediated silencing, specifically the signals initiating this process and the machinery which retains siRNA at its target site.

Stem cells, regeneration and cancer

Upon browsing the preliminary programme of speakers about two weeks before the start of the meeting, I noticed with great delight that a number of lectures would be focused on regeneration. I especially looked forward to Elly Tanaka’s (Technische Universitaet / Center for Regenerative Therapies Dresden, Germany) talk on limb regeneration in two species of salamander, axolotl and newt. She highlighted some fundamental differences in the mechanisms of limb replacement in these two organisms after amputation. I was especially struck, and perhaps a little confused, by the fact that axolotl and newt both belong to the order of salamanders, yet seem to use different mechanisms to regenerate lost appendages.

Focusing in particular on skin, Ben Simons (University of Cambridge, UK) talked about his inquiry into the mechanisms by which skin stem cells maintain their tissue. His lab’s previous work on this topic challenged the accepted theory of skin maintenance at the time. As he explained the validation and alternate experiments they carried out to confirm that their hypothesis was substantiated by the evidence, I became more and more impressed with his work. I felt that it needed a lot of confidence and courage to challenge long-standing theories and a great amount of perseverance to convince other people of the validity of your research. He also talked about the role these skin stem cells in injury repair and in the progression from papilloma to cancer.

With great relevance to my own work, I was also excited to hear about Jyotsna Dhawan’s (National Centre for Biological Sciences, India) research into the factors which mediate reversible quiescence in muscle progenitor cells. She proposed a completely new way of thinking about the G0 stage in cell cycle, suggesting that quiescent stem cells are poised for proliferation or differentiation rather than simply lying dormant. I find particularly intriguing that this may not only be the case in muscle progenitors, but also in other tissue stem cells which remain quiescent in the absence of activation stimuli. She also implicated chromatin-modulating proteins, which may act as a molecular switch.

Further talks included Cathrin Brisken (Ecole polytechnique federale de Lausanne, Switzerland), who presented hear team’s research on the role of progesterone in adult mammary gland maturation and also addressed the significance of hormone mimetics in breast cancer. Moreover, both Anna Bigas (Institut Hospital del Mar d’Investigacions Mediques, Spain) and Sarah Bray (University of Cambridge, UK) talked about the role of Notch signalling in blood cell precursor specification in mouse and Drosophila, respectively.

Patterning and early development

Another highlight for me was Olivier Pourquie’s plenary lecture about the generation and differentiation of the paraxial mesoderm. I had already been familiar with several aspects of his work, but I was surprised to hear a wealth of new findings which looked at the paraxial mesoderm from as many angles as possible. He addressed the oscillatory expression of several genes as somitogenesis takes place as well as remarkable metabolic signatures which differ between anterior and posterior paraxial mesoderm. Further, he spoke about his quest to differentiate induced pluripotent stem cells into paraxial mesoderm in vitro.

The use of unconventional organisms to get to the bottom of evolutionary questions has always fascinated and inspired me. I was thus very interested when listening to Patrick Lemaire (Centre de Recherche de Biochimie MacromoléculaireMontpellier, France) and Robb Krumlauf (Stowers Institute for Medical Research, USA). Patrick presented his work using different genera and species of ascidians, with which he investigates how morphological characteristics can stay stable across time despite major genomic changes. Robb talked about his lab’s research into the evolutionary origins of the Hox clusters using the lamprey. In both their presentations, the speakers highlighted the problems of working with such unconventional organisms and I was particularly intrigued by the fact that many of the conventional techniques in molecular biology can be adapted for these exotic organisms.

Additional talks looked at the migration of precursor cells and their differentiation. Stephen Fleenor (University of Oxford, UK) presented his PhD project on the role of G-coupled proteins in craniofacial ganglion precursor proliferation, migration and differentiation. Moreover, James McColl talked about the role of several signalling molecules in the migration of heart progenitor cells. Lastly, Ferenc Mueller (University of Birmingham, UK) addressed the complexity of promoters and enhancers, which his team investigates through the maternal-zygotic transition of transcription in the early embryo.

“Other”

In this last section, I will focus on several talks which I have not managed to assign any particular topic to. One of the last talks of the meeting was also one I considered among the most compelling. Gero Miesenbock (University of Oxford, UK) presented his work on the role of circadian and homeostatic components in sleep control in a most captivating manner. Using a Drosophila model with sleep deficits, he described his team’s experiments step by step to expose the cause of insomnia. I particularly appreciated the use of a wide range of techniques, including molecular biology, optogenetics and electrophysiology.

As part of the post-graduate symposium, Daniel Hayward (University of Exeter, UK) focused on his research on centrosome-mediated and chromatin-mediated microtubule nucleation. With a focus on moesin and actin, Nelio Rodriguez (University College London UK) presented his work on cell shape changes throughout the cell cycle. Finally, Andrei Luchici (University College London, UK) explored the role of forces in contact inhibition.

All in all…

In my opinion, the BSDB/BSCB spring meeting 2013 was a great success, with a wealth of fascinating talks and posters along with great social events which stimulated conversation and networking. I feel like I have seen and heard a lot of interesting, novel and exciting science and have had the privilege of listening to many inspiring people. This being my first “big” conference experience, I couldn’t have asked for a better meeting to go to and I am already looking forward to next year’s BSDB/BSCD spring meeting.

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Retinoic acid is one of the most important signaling molecules during development, and that the embryo gets the right levels of this small molecule is critical. Too much or too little, and the basic patterning of the nervous system and many other organs goes terribly wrong. Indeed, you have to think for a bit to find an organ whose development isn’t affected by retinoic acid levels.

It’s been thought for a long time that retinoic acid acts through a morphogen gradient. However, because the molecule is small, extremely labile, and not protein-based, it’s been difficult to actually measure its levels in the early embryo. The best visualization of a gradient has come from transgenic zebrafish lines. Perz-Edwards et al (2001) established a line in which the expression of YFP is controlled by a trio of retinoic acid response elements (RARE; a regulatory motif that is activated by a complex of retinoic acid and its receptors). This line was nicely quantified by White et al (2007), and in the hindbrain, where retinoic acid is important for anterior-posterior patterning, you can see a gradient of fluorescent signal. However, the signal is only visible from about 22-24 hours of development, well after basic patterning is already established. Even stringing together 12 RAREs to boost the level of fluorescence isn’t sufficient to make the signal visible much earlier (Waxman and Yelon, 2011).

A new paper in Nature by Shimozono and colleagues uses a clever approach to more directly measure retinoic acid levels during zebrafish gastrulation, when the basic patterning of the nervous system and somites is set up. They took the ligand-binding domain of a retinoic acid receptor and fused it with both CFP and YFP. When the ligand-binding domain binds retinoic acid, its conformation changes and there is a FRET event. Measuring FRET therefore gives you a read-out of retinoic acid levels. They show clearly that a two-tailed gradient is established during gastrulation, but the anterior and posterior sides of the gradient (ie. in the hindbrain versus the somites) differ in their dynamics, shape, and regulation.

A useful aspect of their system is that while previous transgenic lines measure the signaling capacity of retinoic acid, as they depend on transcriptional activity, this method measures the molecule’s absolute levels. Comparing quantities and activity could be useful for the study of how retinoic acid is processed, sequestered, and regulated. Another advantage of their system is that they created versions of the sensor protein that have different affinities for retinoic acid- allowing the measurement of both higher and lower levels of the molecule, depending on what part of the embryo you’re interested in.

Overall, this new tool will be extremely valuable to the research community, and will allow labs to study this key signaling molecule more precisely and directly.

——–

References:

Perz-Edwards, A., Hardison, N., Linney, E. (2001) Retinoic acid-mediated gene expression in transgenic reporter zebrafish. Developmental Biology, 229(1):89–101.

Shimozono, S, Iimura, T., Kitaguchi, T, Higashijima, S., Miyawaki, A. Visualization of an endogenous retinoic acid gradient across embryonic development. Nature (2013), published online April 7, 2013.

Waxman, J. and Yelon, D. (2011) Zebrafish retinoic acid receptors function as context-dependent transcriptional activators Developmental Biology, 352(1):128–140.

White, R., Nie, Q., Lander, A., Schilling, T. (2007) Complex regulation of cyp26a1 creates a robust retinoic acid gradient in the zebrafish embryo. PLoS Biology, 5(11): e304.

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Technische Universität Dresden (TUD) is among the top universities in Germany and Europe: strong in research, offering first-rate programs with an overwhelming diversity, with close ties to culture, industry and society. The TUD is one of the eleven German universities that were identified as an “elite university” in June 2012. As a modern full-status university with 14 faculties it offers a wide academic range making it one of a very few in Germany. TUD is the largest technical university in Germany.
The DFG Research Center for Regenerative Therapies Dresden, CRTD (www.crt-dresden.de) and Cluster of Excellence forms a network of more than 90 research groups working in the areas of Haematology, Diabetes, Neurodegenerative diseases as well as bone regeneration. The CRTD offers a position for an outstanding applicant with international scientific qualification as a

Junior Research Group Leader for Retina Research (up to E 15 TV-L)

This position is available for up to 5 years. The period of employment is governed by the Fixed Term Research Contracts Act (Wissenschaftszeitvertragsgesetz – WissZeitVG).

The aim of the junior research group leader is to pursue basic research into the cellular and molecular mechanisms of retinal degeneration and regeneration using vertebrate animal models like zebrafish or mouse and/or tissue culture. You will join a community of researchers working towards a better understanding of cellular and molecular mechanisms of retinal disease, and to develop cell based methods for restoring retinal function. The successful applicant will be invited to apply, together with the CRTD, for junior group leader funding, e.g. from the Deutsche Forschungsgemeinschaft (Emmy Noether program) or the European Union (ERC starting investigator program). If successful, funding for the Junior Research Group would typically run for 5 years. The period of employment is governed by the Fixed Term Research Contracts Act (Wissenschaftszeitvertragsgesetz – WissZeitVG). The new research group will be housed in a new state-of-the-art building equipped with excellent core facilities located on the Life Science Campus, next to the Biotechnology Centre (www.biotec.tu-dresden.de), the Max-Planck-Institute for Molecular Cell Biology and Genetics (www.mpi-cbg.de), as well as the “Dresden International Graduate School of Biomedicine and Bioengineering” (www.digs-bb.de) and the Dresden University Hospital Carl Gustav Carus (www.uniklinikum-dresden.de).

TU Dresden seeks to employ more women in leadership positions. Hence we should particularly like to encourage qualified women to apply. Applications from disabled candidates or those with additional support needs are welcome. TU Dresden is a family-friendly university and offers a dual career service.

Applicants must have a university degree in natural or medical sciences, a doctoral degree and an outstanding international scientific track record.

Please send your application forms, including a CV, a publication list, description of past and future research activities, acquired third-party funding, and two letters of recommendation by 16.05.2013 (stamped arrival date applies) preferred via e-mail (PDF) to sabine.matthiae(at)tu-dresden.de (Please note: We are currently not able to receive electronically signed and encrypted data) or to TU Dresden, DFG-Center für Regenerative Therapien Dresden, Cluster of Excellence, Director CRTD, Prof. Dr. Michael Brand, Fetscherstrasse 105, 01307 Dresden, Germany.

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Before I even start to tell you anything about this year’s BSCB/BSDB Joint Spring Meeting, I would like to apologise to you if you expect this post to be a detailed description of the science presented there. As tempting as that was, I forced myself no to do it because I wanted to give you a feeling of the general atmosphere of the conference and about the people that were there. Having said this, please get comfortable in your seats and put your seat belts on because we are about to prove Einstein wrong and travel back in time!

It was 8.30am and after spending a late night at the postgraduate social event, I found myself in the Arts centre of Warwick University. From the moment I first entered the building I could not restrain myself from noticing that the air was filled with the smell of freshly ground coffee. For some unknown reason this smell gave me a sudden urge to go and buy a cup of the energising liquor. As I was standing there, I looked around and I realised, to my surprise, that the place was already swarming with people finding their way to the first session of the conference. After getting some coffee, I dragged my half asleep feet and joined another queue… this time it was the queue to the lecture theatre where the Epithelia and Mechanosensing session was about to begin.

After a brief introduction to the conference beautifully delivered by Dr Jim Smith, it was time for the hard-core science to begin. The first round of talks was opened by Dr Barry Thompson who’s talk helped me (an engineer working in biology) understand how well regulated is the epithelial polarity. Using Drosophila as a model organism and a combination of genetics, molecular biology and computer modelling techniques, he discovered that apicobasal polarity requires a combination of positive feedback among apical determinants and mutual antagonism between apical and basal determinants. Wow! It must have been Barry’s presentation skills that made this last sentence have perfect sense at that time because as I write this I realise that things are much more complicated!

Following from this really successful interdisciplinary effort, Dr Pierre-François Lenne changed the tone of the session by presenting how the interaction between actomyosin network and adhesion complexes creates mechanical forces during tissue morphogenesis. Again using Drosophila as a model organism, Pierre employed confocal microscopy to directly measure cortical forces during embryo elongation and to investigate how adhesion complexes, especially E-cadherin, are capable to generate and respond to mechanical cues.

The last talk of this morning session tried to address how could synthetic biology and biomimetics help answer questions that are relevant for in-vivo systems. Jenny Gallop has managed to successfully recreate filopodia-like structures in vitro using only artificial membranes and frog egg extracts to recapitulate the actin signalling pathway required to produce these structures. After having to take in so much new information, it was now the time to go and recharge our batteries for the next sessions. As people started to form another seemingly interminable queue for coffee, I could see and hear that everywhere around me people were still discussing about the science presented in the talks we have just heard.

During this break you could see how the swarming I saw in the morning came to a rest. Everyone was still puzzled about how cells can generate, transmit and understand mechanical forces, so we were hanging around in groups discussing about mechanotrasduction and its roles inside a living organism. As it always happens when you engage in a passionate conversation, during that morning too, time passed so fast that we barely realised that the break was over and it was now time to head back towards the lecture theatres for the second part of the morning session.

Dr Shigenobu Yonemura opened the second part of this session. His talk was a perfect fit for what I kept asking during the break: how are different proteins sensing force? In the short time he had available, he managed to give me an answer to my question using alpha-catenin and adherens junctions as a practical example.

Changing scales, it was Daniel Grimes’ turn to further illustrate the roles of forces in development. His work managed to show how essentially a 1D structure, cilia, are capable of creating 3D left-right asymmetries during mice embryo development. Following the same trend, Katja Roper works on tubulogenesis of the Drosophila salivary glands revealed how an anisotropy in plasma membrane distribution of a protein, Crumbs, determines the subcellular localisation of a supracellular actomyosin cable in the cells at the pacode border.

There could not have been a better way to end this session than Dr Guillaume Charras’ talk on how physical sciences, especially nanotechnology, are capable of offering new tools and techniques to analyse biological systems. His brief survey of microfluidics and atomic-force microscopy combined with practical applications of each technique succeeded to point out how engineering and biology could work together to advance our understanding of the differences between animate and inanimate matter.

During lunch, the swarming I saw as I was waiting in the queue to buy myself a cup of coffee in the morning reappeared, only now people were buzzing around posters. This provided a good opportunity for everyone to mix and meet other people. After a while the swarming calmed down as it was now time to head to the second session of the day on Motors and Morphogenesis.

As I expected, this session was mind-blowing; all speakers presented cutting edge research at the interface of cell biology, developmental biology and engineering. Out of a very impressive pool of speakers, there was one that clearly set the tone of each part of the session. In the first part, I was very impressed by Dr Darren Gilmour’s talk on how zebra fish lateral line primordium (a migrating epithelium) is capable to generate its own local gradient of chemokine to power its collective migration.

Exactly when I thought that I finally got an idea of how cells integrate biochemical pathways and mechanical cues, Dr Jennifer A. Zallen brought back one question on mechanotransduction that I tried to answer for myself, but failed every single time: how local changes in cell architecture can generate long range effects in a tissue? Using Drosophila embryos as a model organism it was possible for her to show that asymmetries in contraction and adhesion and a mechanical feedback loop are all the ingredients needed to reorganise the cells during body axis elongation. I was impressed by the simplicity of this mechanism that cells use to transmit forces at a distance compared to its complex role during development.

As this was not exciting enough, the afternoon session offered me another pleasant surprise as Prof Kate Nobes and Mr John Robert Davis presented two different roles for contact inhibition of locomotion. First Prof Nobes showed how invasive cancer cells change their biochemistry and fail to contact inhibit in vitro. In a completely different system, Drosophila hemocytes (macrophages), John clearly demonstrated that contact inhibition of locomotion is the major driver of the even hemocyte dispersal during embryo development in vivo. These seemingly different talks made me think how magnificent biology is… once cells find an efficient mechanism for performing a function they stick to it and even transfer it from one cell type to another or from one species to another with virtually no major modifications. This gives a completely different meaning to cross-scales communication and for an engineer this is simply mind-blowing!!! I know this starts to become somehow philosophical, but I couldn’t help myself to wonder about it while I was sitting in the back of that half lit lecture theatre and listened to so many examples of this communication across scales.

Unfortunately it all finished too fast, at least that’s how I felt it, because the next thing I remember it is how I was finding my way to the cafeteria to have dinner with a lively group of people which I already knew or have just met there. We were all exchanging our opinions about the science of that day and then suddenly began to discuss a SciFi topic… how we could engineer artificial cells to perform any task we want them to? This continued for a while until everyone decided that it was about time to go and have the first pint of the night and then to head for the memorial lectures.

After this we were all a little tired, and most of us just wanted to call it a day, but we had no idea what surprise was waiting for us as we waited for the Waddington Medal talk: Sir John Gurdon has kindly agreed to come to the meeting and he was sitting there mysteriously waiting to see who has won this years medal. If that was not enough, organisers had another ace down their sleeve… Jim Smith won the Waddington Medal for his fruitful career as a developmental biologist and gave a very inspiring and entertaining talk about his science and his life! Through his stories he managed to convey how much science has changed over the past three decades… from the days when any result was a good result (it did not have to be only a positive one to be considered valuable science) and when it sometimes took as long as six days to get published in a highly respected journal, to the present when it could take up to a few years to get one publication(and that cannot be a negative result!).

This last talk crowned the day, but I think it also did much more… Jim managed to wrap up a very informative first day of the conference and inspired the next generation of cell and developmental biologists to pursue their passion despite any hardship that comes in their way!

(3 votes)

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Here are the highlights from the current issue of Development:

Dynamics of human thymus development

The thymus is the primary organ responsible for generating T cells. Although thymus development has been studied in mice, little is known about how the human thymus develops. Here (p. 2015), Clare Blackburn and colleagues provide a comprehensive analysis of human thymus organogenesis. Using gene expression analyses, the researchers show that the spatial and temporal expression patterns of factors involved in thymus development in mice are conserved in humans. They also demonstrate that the human thymus arises from the third pharyngeal pouch, as in mice and in contrast to previous suggestions. Furthermore, they report, thymic epithelial cell differentiation as well as the immigration of mesenchymal cells and vascular progenitors into the human thymus occur after the onset of FOXN1 expression, consistent with the timing of these events in mice. Finally, the authors define precisely when the human thymus becomes colonised with haematopoietic cells, which are CD45⁺/CD7⁺/CD34^int cells. Collectively, this study provides key insights into the conservation of thymus development between mice and humans, which has major clinical implications for enhancing or replacing thymus function.

Coordinating head-to-tail with front-to-back

During embryogenesis, the anterior-posterior (AP) and dorsal-ventral (DV) axes are specified by the activity of key signalling pathways. FGF, Wnt and retinoic acid together pattern the AP axis: high activity defines more posterior tissues, which are specified later in development than anterior tissues. The BMP pathway specifies ventral fate; low BMP activity defines dorsal. Whether and how these pathways intersect to coordinate patterning of the two axes is poorly understood. On p. 1970, Megumi Hashiguchi and Mary Mullins provide evidence for synchronisation of DV and AP patterning in the zebrafish embryo. Upon temporally restricted inhibition of BMP in embryos anteriorised by inhibition of FGF or Wnt, the dorsalised tissue takes on the AP fate appropriate to the anteriorised embryo, rather than that corresponding to the time of BMP inhibition. The authors identify one mechanism mediating pathway cross-talk: MAPK, activated downstream of FGF, phosphorylates and inhibits the BMP effector Smad5. Thus, this work establishes the close temporal coordination of AP and DV patterning, and provides insights into how this is achieved.

miR-203 drives progenitor cell differentiation

MicroRNAs are important for the regulation of gene expression in a vast array of processes. In the skin, miR-203 has been shown to be crucial for the proper differentiation of the interfollicular progenitor cells, although the specific mechanism of this has remained elusive. In this issue (p. 1882), Rui Yi and colleagues investigate the precise timing of miR-203 activation during epidermal differentiation. They show that miR-203 is transcriptionally activated in the differentiating progeny of interfollicular progenitor cells upon asymmetric cell division. Using keratinocytes derived from miR-203-inducible mice, the authors found that miR-203 functions to promote an immediate exit from the cell cycle, leading to a complete loss of self-renewal after just 72 hours. They further identify a multitude of novel miR-203 targets in vivo, and demonstrate that co-repression by miR-203 of many of these, including Skp2, Msi2 and p63, is necessary for the function of miR-203 in inhibiting self-renewal. These data provide novel insights into the widespread role of miR-203 in differentiating interfollicular progenitor cells in the skin.

Leaf patterning: AS1 far AS2 we know

The correct establishment of adaxial-abaxial patterning is crucial for leaf expansion and growth. The AUXIN RESPONSE FACTOR (ARF) family of proteins are key determinants of organ symmetry and abaxial patterning in Arabidopsis thaliana and are subject to complex regulatory control at both the transcriptional and translational level. Here (p. 1958), Chiyoko Machida and colleagues uncover an additional, dual mechanism for the regulation of ETT (also known as AFR3) by an ASYMMETRIC LEAVES1 (AS1)-AS2 complex. First, the authors show that the AS1-AS2 complex directly represses ETT expression via binding of AS1 to the promoter region. Second, they provide evidence for an indirect mechanism of regulation via miR390- and RDR6-dependent post-transcriptional gene silencing of both ETT and ARF4. The authors also suggest a possible epigenetic mechanism, as AS1-AS2 maintains the methylation status of ETT within the coding region. These discoveries shed light on the molecular framework of early leaf patterning events and help to uncover the events that lead to the specification of distinct adaxial and abaxial fates during leaf development.

PAR-alell pathways for polarity

In the C. elegans embryo, anterior-posterior polarity is defined at the one-cell stage, via asymmetric and reciprocal localisation of cortex-associated PAR protein complexes: PAR-3, PAR-6 and aPKC localise to the anterior, whereas PAR-1, PAR-2 and LGL-1 are enriched at the posterior. Polarity maintenance involves mutual antagonism between the anterior and posterior complexes and may also involve CDC-42-dependent regulation of myosin activity. Kenneth Kemphues and co-workers (p. 2005) now provide evidence for multiple and partially redundant pathways acting at the posterior to maintain polarity once it has been established. Both PAR-2 and CDC-42, acting in separate pathways, have dual functions in independently regulating both anterior PAR complex localisation and myosin activity, whereas LGL-1 appears to have a buffering role in controlling PAR-6 protein levels. Although the molecular details of these pathways remain incomplete, the complex and overlapping mechanisms operating to maintain polarity in the early embryo underscore the importance of robust and efficient polarisation for subsequent development.

Stem cells go out of bounds

Many animal tissues maintain populations of slowly proliferating stem cells that contribute to tissue homeostasis and repair. In Drosophila, for example, stem cells reside throughout the midgut and within the hindgut and renal tubules. But how and when do these cells arise? Volker Hartenstein and colleagues now show that Drosophila gut progenitors migrate across tissue boundaries and adopt the fate of the organ in which they come to reside (p. 1903). Using lineage tracing, the researchers demonstrate that a subset of adult midgut progenitors, which are initially located in the larval midgut, migrate posteriorly during development and contribute to the adult ureter and, subsequently, the renal stem cell population. In addition, they report, a population of hindgut progenitors migrates anteriorly into the midgut territory to differentiate and give rise to midgut enterocytes. These findings suggest that a stable boundary between the midgut (an endodermal tissue) and the hindgut/renal tubules (ectodermal tissues) does not exist and instead multipotent progenitors are able to cross the boundaries between these domains.

Plus:

Molecular pathways regulating mitotic spindle orientation in animal cells

Orientation of the cell division axis is essential for both symmetric cell divisions and for the asymmetric distribution of fate determinants during, for example, stem cell divisions. Lu and Johnston review both the well-established spindle orientation pathways and recently identified regulators to provide a updated view of how positioning of the mitotic spindle occurs. See the Review article on p. 1483

Getting out and about: the emergence and morphogenesis of the vertebrate lymphatic vasculature

New insights into lymphatic vascular development have recently been achieved thanks to the use of alternative model systems, new molecular tools, novel imaging technologies and a growing interest in the role of lymphatic vessels in human disorders. Here. Hogan and colleagues review the most recent advances in lymphatic vascular development, with a major focus on mouse and zebrafish model systems. See the Review article on p. 1857

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[Ed. comment: This is the first of a number of posts by a few people who attended this year’s BSDB/BSCB meeting. Look out for more on the meeting over the coming days]

As every year, the joint BSDB/BSCB spring meeting was taking place on the 17th – 20th of March 2013 on the vast campus of Warwick University. Over three days, an exciting line-up of speakers presented their latest research findings, accompanied by more than 200 scientific posters on display!

Among the first events of the conference was a workshop focused on alternative careers for scientists, mainly aimed at PhD and early post-doctoral researchers. Five speakers gave an insight into the paths they have taken since finishing their PhDs and talked about their current positions.

Jana Voigt, currently a research strategy analyst at the University of Cambridge, spoke about her contact with pharmaceutical consulting, which she jokingly called “the dark side”. She then mainly focused on her experience as a research programme manager at the MRC, where she was responsible for dealing with funding applications and reviews.

Ann Wiblin is a business development associate at Abcam at the moment. She described her responsibility in selecting, testing and managing Abcam product lines and also gave valuable advice to those who aspire to this career. Most notably, she recommended learning as many scientific techniques as possible and stressed the importance of networking.

Roli Roberts, currently associate editor at PLOS Biology, called himself a “recovering academic”. After going all the way from his PhD to a senior lecturer position at King’s College London, he decided that he “wasn’t having much fun anymore”. In his current role, he mostly handles manuscripts submitted to the journal, assesses their quality and arranges peer review. For people who want to enter this industry, he pointed out that publishers prefer to hire candidates with several years of post-doctoral experience.

Daniela Peukert is currently a science policy officer for the Society of Biology, where she provides evidence-based opinions for the government and funding bodies, for example in policy decisions. This involves interacting with experts of different fields of biology and arranging meetings with those who seek information. Her main advice was to remain flexible, since she was confronted with many new situations and unfamiliar tasks in her position.

Sam Gallagher introduced her talk with a slideshow of her career to date and the rock song “Summer of ’69” by Bryan Adams. From hereon, her talk boiled down to “Dear god, what did I think I was doing?” as she walked the audience through her career in academic research, the pharmaceutical industry and consulting. As one of the key ingredients to a successful career, she emphasised the importance of taking responsibility and stepping up.

I was particularly impressed with the breadth of careers and personalities that the organisers recruited for this workshop. Each individual entered their line of work in a different manner, but all stressed that it is critical to think outside of one’s own specialised field of research. Every speaker highlighted their broad interest in science, which is rarely compatible with research in academia. Moreover, many took on responsibilities which had little to do with their PhD or post-doctoral work, such as organising meetings, becoming involved in societies and volunteering. The most important message that I took away from this workshop is that there is a life outside of academia and that job opportunities do exist for those science-lovers who do not wish to spend their careers writing grants or managing a lab.

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We had another busy month on the Node, with posts and comments relating to research articles, upcoming meetings, resources for developmental biologists…and, of course, the stem cell image contest.

Here’s a round-up of some of the highlights:

Stem cell image contest

Voting for the stem cell image contest opened earlier this month, and we’ve had close to 2000 votes in so far. It looks like a close race between a couple of the images – which is your favourite? Get your vote in if you haven’t done so already! Voting will close at noon GMT on Wednesday 10th April.

The winning image will appear on a cover of Development as well as on the new stem cell pages we’re developing for the journal’s website.

Research

– Over the last couple of years, Kim Cooper (a post-doc in the Tabin lab) has been providing us with updates (see her intro post here) from her multiple trips to China, during which time she has been collecting jerboas. This month, Kim shared with us the news of the first research article using jerboas to answer a fundamental question in developmental biology.

– Cat Vicente highlighted an cracking (!) paper on the development of crocodile head scales.

– We heard more about a recent paper that identified hair cell progenitors in the postnatal cochlea.

Resources

As always, the Node  proved to be a great place to find and share useful resources. This month we were introduced to:

– an updated toolkit of stem cell resources.

– CiteAb: a search engine for antibodies.

– PostPostDoc: a website for PhDs and postdocs.

Meetings

Mariana Delfino-Machin reported back from the RIKEN CDB Symposium: “The Making of a Vertebrate”

A number of upcoming meetings were also announced:

– the EMBO Workshop on Morphogen Gradients

– a Wellcome Trust meeting on Regenerative Medicine

– a University of Maine Developmental Biology Teaching Workshop

Finally, it was also a busy month in terms of job postings – a good sign really, in light of the current economic climate. To see the most recent job ads, click here. Don’t forget that it’s easy to post a job advert…or anything else that is relevant for the community…simply register and get posting!

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POSTDOCTORAL POSITIONS are available to study the cellular and molecular processes controlling the early development and patterning of the brain and visual system using in vivo mouse models and organ culture systems.

Highly motivated individuals who recently obtained a PhD or MD degree and have a strong background in developmental neurobiology are encouraged to apply. Interested individuals should send their curriculum vitae, a brief description of their research interests, and the names of three references to:

Guillermo Oliver, PhD

Member

Department of Genetics

St. Jude Children’s Research Hospital

262 Danny Thomas Place,

Memphis, TN 38105-3678

E-mail: guillermo.oliver@stjude.org

http://www.stjude.org/oliver

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