We are in our last week of the Embryology Course at Wood’s Hole now, and currently working on annelid and squid embryos. Things are still going at a frenetic pace but I’d like to take this chance to talk a little more about some of the work we did using vertebrates.

The course covers many vertebrate model organisms such as mice, chick, frog and zebrafish but we were also able to carry out some work on other organisms like sticklebacks, bats and even turtles! This was mostly thanks to Richard Behringer who brought an amazing array of different embryos for us to experiment on. On the left you can see a beautiful lizard, which I stained with alcian blue to show cartilage and alizarin red to show bone. This was particularly interesting for me as I am working on the development of the sternum for my Ph.D. project, so it was great to be able to see the morphological diversity in the sternum between species.

To complement the study of this wide range of species, we also revisited some classical experiments carried out in chick and frog to illustrate a number of key developmental principles. One example was the Spemann-Mangold organizer graft in Xenopus laevis, which involves transplanting the dorsal marginal zone of an early gastrula stage embryo into the ventral region of an intact embryo at the same developmental stage. This tissue has the capacity to organize surrounding tissues to form a dorsal axis, so this experiment should generate a tadpole with a secondary axis. Although this required a lot of patience and very steady hands, a few people in the class did successfully grow some two-headed tadpoles!

I wasn’t one of the lucky ones to grow a monster tadpole, but I did get some interesting results for a project I carried out with others in the class working on the establishment of the dorso-ventral axis. We used lithium chloride treatment to dorsalize embryos, and UV irradiation to ablate the dorsal axis. The resulting tadpoles were very messed up, and it was interesting to see which features were lost and which were radialized after each treatment.

We also tried out some transplantation and bead insertion experiments in chick embryos, and used whole embryo and organ culture in mouse. Now the course is drawing to a close and we are trying to frantically gather together and organize all of the data we have on so many of different microscopes. Hopefully I can make some sense of it all and I’ll write back with an overview of the entire course once I’m back in London.

Sorrel

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Here are the highlights from this week’s issue of Development:

Lymphatic networks follow arterial lead

The vertebrate lymphatic system consists of lymphatic vessels, which collect fluid from the tissues and return it to the blood, and lymph nodes, which are involved in immune defence. Lymphatic vessels, like blood vessels, form a complex vascular network, but what guides the development of this network? According to Stefan Schulte-Merker and co-workers, arteries provide crucial guidance cues to the lymphatic endothelial cells (LECs) that form the lymphatic network in the zebrafish trunk (see p. 2653). Using transgenic zebrafish lines that allow the direct visualization of arteries, veins and lymphatic vessels in single embryos, the researchers show first that intersegmental lymphatic vessels (ISLVs) in the zebrafish trunk align with arterial intersegmental vessels (aISVs) but not with venous intersegmental vessels. Then, using time-lapse confocal imaging, they show that LECs migrate exclusively along aISVs and that LEC migration is blocked in zebrafish mutants that lack aISVs. Together, these data reveal a crucial role for arteries in LEC guidance; future research will unravel the mechanism underlying this guidance.

Flowering plant fertilization model over turned

Fertilization in flowering plants involves two sperm cells and two female gametes – the egg cell and the central cell, progenitors of the embryo and endosperm, respectively. A previous study suggested that Arabidopsis plants carrying loss-of-function mutations in cyclin dependent kinase A1 (CDKA:1) make a single sperm cell that preferentially fertilizes the egg cell to produce an embryo that triggers central cell division. Now, Frédéric Berger and colleagues overturn these widely accepted results by showing that a significant proportion of cdka;1 pollen actually delivers two sperm cells (see p. 2683). Delivery of a single cdka;1 sperm cell to a wild-type ovule can fertilize either female gamete, they report. However, when two cdka;1 sperm cells are delivered, one fertilizes the egg cell and the other activates central cell division. Fusion of the gamete nuclei fails in the central cell, however, which prevents paternal genome incorporation and causes seed abortion. Thus, this new analysis of the cdka;1 phenotype reveals an essential role for the paternal genome during early seed development.

Med(12)iating Wnt signalling in mouse development

Mediator, a conserved multiprotein complex that connects DNA-bound transcription factors to the RNA polymerase II machinery, is part of the intricate mechanism that regulates eukaryotic transcription. The Med12 mediator subunit is required for gene-specific functions during zebrafish development, but are its developmental functions conserved in mammals? On p. 2723, Heinrich Schrewe and colleagues address this question by examining embryos generated from mouse embryonic stem (ES) cells in which Med12 has been targeted. Embryos generated from Med12 hypomorphic ES cells fail to develop beyond embryonic day 10, the researchers report, and have severe defects in neural tube closure, axis elongation, somitogenesis and heart formation. The Wnt/planar cell polarity pathway and canonical Wnt/β-catenin signalling are both disrupted in the Med12 hypomorphic embryos, they note. Furthermore, embryos generated from Med12 null ES cells fail to establish the anterior visceral endoderm, activate brachyury expression or complete gastrulation. Together, these results indicate that Med12 is necessary for gene-specific functions and for correct Wnt/β-catenin and Wnt/PCP signalling during early mouse development.

Mechanics of morphogenesis revealed

The morphogenetic movements that shape embryos depend on the forces generated by embryo’s cells and on the resistance of its tissues to these forces. Microtubules and F-actin are largely responsible for both these cellular properties but the contribution of these structural elements to morphogenesis is unclear. Now, Lance Davidson and colleagues unexpectedly report that nocodazole-induced depolymerization of microtubules stiffens the converging and extending dorsal tissues in Xenopus embryos (see p. 2785). The researchers attribute this result to the release of Xlfc – a guanine exchange factor that binds to microtubules and that regulates actomyosin contractility by activating Rho family GTPases. Consistent with this idea, drugs that reduce actomyosin contractility rescue nocodazole-induced embryonic stiffening and partly rescue the morphogenetic defects of stiffened embryos. Other experiments that combine drug treatments and Xlfc activation and knockdown indicate that microtubules have no direct role in maintaining bulk tissue stiffness in Xenopus embryos. The researchers conclude, therefore, that microtubules indirectly regulate the mechanical properties of embryonic tissues through RhoGTPase pathways.

Bicoid gradient: precision through hunchback

Morphogenetic gradients determine cell identity during development through the concentration dependent activation of target genes, but how the precision of the response to morphogens is determined is unclear. On p. 2798, Nathalie Dostatni and co-workers provide new insights into this developmental puzzle by examining the transcriptional response to Bicoid in Drosophila embryos. The Bicoid gradient is established in Drosophila embryos after eight nuclear divisions (cycle 9) and target protein expression is specified by cycle 14 with a precision that corresponds to a 10% Bicoid concentration difference. To understand how this precision is achieved, the researchers analyze nascent transcripts of the Bicoid target gene hunchback. They report that hunchback is already transcribed from both alleles in most anterior nuclei in cycle 11 interphasic embryos. This synchronous expression is specified within a 10% difference of Bicoid, a precision that is compatible with the fast mobility of Bicoid in the nucleus measured using fluorescent correlation spectroscopy. Finally and importantly, genetic experiments reveal that maternal Hunchback contributes to the early synchrony of the Bicoid response.

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Greetings!
It’s been an overcast, windy and gloomy Monsoon here in Bangalore, but the past few weeks at NCBS have been bright and exciting! The “Maggot Meeting – 2010”: Neural Circuits and Behaviour is currently on till the 27th of July and I look forward to the seminars and interactive discussions with eminent scientists. Early last week the Center hosted the EMBO Global Exchange Lecture Course on ‘Systems neuroscience of the Drosophila larva: genetic and circuit bases of behaviour’. This series of lectures and demonstrations were devoted to the basics of neuroscience, development and behaviour. I was invited to participate as a Teaching Assistant to demonstrate live cell calcium imaging in Drosophila melanogaster primary neuronal culture. I am very pleased to have been given this opportunity to share my training and knowledge on new methods and techniques with other fellow participants. It has truly been a wonderful experience!

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There was a nice piece on the Naturejobs site this week, written by postdoc Katherine Sixt. She describes how she started to realize that not every postdoc will eventually become a professor. There simply aren’t enough positions available, so postdocs should look at other careers. But as a postdoc, and even as a PhD student, you are being trained as if you were aiming for a job similar to the one your supervisor has, and anything else is considered strange and different. Katherine writes: “I feel as though I have to sneak off to careers seminars where scientists describe their non-traditional paths. Thoughts of alternative career choices are still dirty secrets for some.”

Over the past few years, I’ve read many similar articles. Some from the position of the postdoc looking for work, others more reflective and distant – considering ways in which to deal with the simple truth that there are far more postdocs than there are academic positions for them to fill.

What do you think: Should there be fewer postdoc and PhD positions? Or different kinds of trainee positions, where some include training for scientific careers outside of the lab? Have a read through the following articles and blog posts to see what others have to say about it:

In Which I Dream of Revolution – Jenny Rohn
Quote: “Yesterday morning I woke up and realized that the entire logistical edifice underpinning the scientific profession is flawed. What’s more, I didn’t just see the problem; I had a glimpse of its solution.”

Do We Produce too Many Biomedical Trainees? – Jeff Sharom [Link to PDF]
Hypothesis Journal, 6(1), 17-29 (2008)
This is a review article that looks at evidence for and against the idea that there are too many trainees.
Quote: “Paradoxically, while research aims to recruit rational individuals, research may not be a rational career choice”

Are we training too many scientists? – Bijal Trivedi (in The Scientist, 2006)
Quote: “With rising numbers of newly minted life science PhDs, fewer tenure track positions open, and bulging ranks of increasingly frustrated postdocs, many want to know why the number of PhDs and the focus of their education is out of balance with job prospects and career expectations.”

Are there too many PhDs? – Jason Hoyt (on the Mendeley blog)
Quote: “Only then, do students realize the road that lies ahead is dotted with pit stops leading, not to Nobel glory, but a journeyman career with salaries well below that of their friends who went into business, law, or medicine.”

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If you’re annoyed by the unconvincing lab work on shows like CSI, and would like to show the world what real scientists are like, why not make a film yourself? You’d be surprised to find out how many films by or with scientists there are, both fiction and non-fiction. This month alone, two organizations involved with science films have either screened or collected a number of submissions, and I also recently found out that one of my favourite documentaries (about the daily life and careers of science graduate students) is available to view online.

Last week, Planet SciCast screened the winners of a competition in which schools and scientists had made fun and informative films about science. All submissions are available to watch on their website, and the awards ceremony was held at the Royal Institution in London last Friday. If you liked the plasticine embryo model previously featured on the Node, you might also enjoy this stop motion clay video about mitosis at Planet SciCast.

While the SciCast films are predominantly factual and made by students, the Imagine Science Film Festival in New York is currently collecting a wide range of both amateur and professional, fictional and factual, films for their annual festival in October. Their late deadline is on August 15, so if you happen to have a film lying around, you can still submit it. Last year my own tiny five-minute film about Lab Waste screened in the ISFF “quirky shorts” program, and I was impressed with all the other (far more professional!) films that were shown that night. ISFF lasts more than a week, and screens full length films as well as shorts.

ISFF promotes interaction between scientists and film makers, and many of their submissions are made by film professionals, but involve scientists as main characters or writers or consultants. My favourite film that I saw at ISFF last year was a French film called MEPE, which also won one of the festival’s awards.

MEPE, a French detective film about biology… It’s entirely in French and this version is unfortunately without subtitles, but even if you don’t speak the language you can appreciate the style and quality, and maybe even some of the humour.

My own little movie (more a slideshow…), which screened on the same night as MEPE at ISFF last year, is quite literally a work of garbage, and a completely different kind of film, so you can see the variety at ISFF – even within one evening of programming.

Lab Waste from Eva Amsen on Vimeo.

If film festivals, artsy French dark comedy, school projects, or pictures of garbage are not your thing, then you might still be interested in watching the full-length documentary Naturally Obsessed about three graduate students in Larry Shapiro’s lab at Columbia University in New York.  No matter what you’re working on and no matter where you are in your career – whether you’ve just started graduate school or finished long ago – you have to see this film. The three students are completely different, and you’ll undoubtedly identify with at least one of them and understand their frustrations and/or celebrations. It’s available to watch online.

All these films involved working scientists either as subjects, producers, advisers, or judges, so there are lots of opportunities to get involved and do your part to represent science on screen.

(1 votes)

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On July 9, the editors of Development met in Strasbourg (or joined over the phone) for a meeting. Because Development‘s editors are spread out all over the world, these meetings are a rare opportunity to get everyone together to discuss the journal. Editors all get a chance to share ideas they have for the journal, and discuss what is happening in their respective fields.

The meeting was also a great opportunity to get some Development editors and The Company of Biologists directors in a photo together:

From left to right: Eva Amsen (Online Editor, the Node), Austin Smith, Seema Grewal (Reviews Editor), Olivier Pourquié (Editor in Chief), Rong Li, Steve Wilson, Claire Moulton (The Company of Biologists, Publisher), Ken Zaret, James Briscoe (The Company of Biologists, Director), Kate Storey (The Company of Biologists, Director)

Our Editor in Chief, Olivier Pourquié, is director of the IGBMC just outside of Strasbourg, so he was kind enough to offer us meeting space there. Those of us who arrived in Strasbourg the day before had a bit of time to explore the city and enjoy a nice dinner on the eve of the meeting.

It was a productive meeting (when we figured out how to work the speaker-phone for the conference callers!) and we all went back with lots of new ideas for the journal. The Node was also on the program, and I was able to show the first two weeks of Node statistics and feedback. I got some suggestions and ideas for topics and features on the site, so you’re hopefully all benefiting from this meeting in a very indirect way!
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(This interview by Kathryn Senior originally appeared in Development on July 13)

Thomas Lecuit heads up a multidisciplinary team of 10 scientists at the Developmental Biology Institute of Marseilles (IBDML) in France. He is deeply interested in how the tissues that form our organs acquire and maintain their proper architecture and has special expertise in the physics and modelling of embryonic development. He has been an editor of Development since 2008. Thomas kindly agreed to an interview to tell us about how he got started in science, and about his passion for work, music and sleep…

When did you first realize you were interested in science?

For as long as I can remember, I have always been trying to understand the world around me. I firmly believe that detailed observation and abstraction are essential for understanding. I have a strong memory from when I was 11 or 12 of reading a book about plate tectonics and of being fascinated in how the oceans and continents form. It opened my eyes to the work of scientists and that they can explain phenomena that are far removed from everyday experience. As a kid, I spent a lot of my spare time looking for butterflies and plants, trying to recognize closely related species. I didn’t know that I wanted to be a scientist then, but I realized much later that I was already behaving like one.

Who inspired you to follow a scientific career?

My greatest early mentor was my grandfather. He was a true naturalist, and when I was about 10, he began to educate my sense of observation, teaching me Linnaean classification, focusing on my interest in butterflies. I was lucky that he took my childhood hobby very seriously and helped me rationalize it. I remember him giving me scientific articles about natural butterfly hybrids from the southern Alps, which he had characterized. He also told me about his accidental discovery of a new butterfly phenotype that bred true and that he showed to be due to a dominant mutation. This was extraordinary to me and had a major influence – I think my later career in science owes much to these early experiences.
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Three weeks ago, we joined a group of twenty-four students from around the world arriving in the small town of Woods Hole, Massachusetts. We were strangers from all sorts of backgrounds, but we were drawn together by one commonality – a deep interest in developmental biology. We are all here to participate in the Marine Biological Laboratory’s Embryology course – an intensive six-week program that is in its 116^th year.

The class approaches developmental biology from many perspectives using numerous model and non-model organisms. Each week is structured around a different group of animals, learning the biology and techniques which can be used to study each species, from cnidarians to flies to worms to frogs (and many more!). A typical day starts with a morning lecture presented by a leading scientist, who describes his or her research in the context of the development of the study organism. Following lecture, we have a student driven discussion. Over the years this has come to be known as the “sweat box” because of the probing nature of the questions asked by the students! In the afternoon, lab section begins, and we keep working until late into the night learning new techniques for each organism, as well as using a range of imaging techniques to visualize our results. The students also design and carry out our own research projects, which is the most exciting part of all!

Introduction to each of our research interests:

Laurel Hiebert: I am a second-year graduate student at the Oregon Institute of Marine Biology, University of Oregon, where I am studying the emergence of antero-posterior patterning in a novel larval body plan – the pilidium larva of marine ribbon worms (phylum Nemertea). I have broad interests in evolution of morphological diversity, and I am particularly excited about the opportunity to learn about development in a great variety of organisms.

Sorrel Bickley: I work at the National Institute for Medical Research in London, where I am in the first year of my Ph.D. studying the development of the limbs and the pectoral girdle. I am broadly interested in organogenesis and the processes and pathways that regulate cell differentiation and migration to form a functioning structure. In my lab I work with chick and mouse, so I am excited about the opportunity to try out new techniques in these organisms as well as learning about other species.

Ann Grosse: I am a graduate student in Deborah Gumucio’s lab at the University of Michigan. I study the morphogenetic changes responsible for remodeling the embryonic mouse intestinal epithelium to form a functional absorptive epithelial layer. More generally, my interests include answering embryological and developmental questions of cell polarity, shape, and movement using animal models, live imaging, genetic manipulation, and developmental techniques. Because I will soon be graduating, I am excited to interact and learn from faculty and students who are leaders in their respective fields. Experimentally, I look forward to the animal models most suited for live imaging: C. elegans, Xenopus, zebrafish, and sea urchin.

We will update this blog each week to discuss the work we have been doing on the course and also to show some of the images we have captured. As an introduction we would like to share this beautiful grasshopper embryo image, which was stained with an Ultrabithorax antibody (in red) and DAPI (in blue). We are very thankful to the Company of Biologists, who provided scholarship funds for the three of us.

(2 votes)

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The Node has been officially live for almost four weeks now, and we’ve seen visitor numbers and registrations go steadily up. As with most websites, there are far more silent readers than people who are actively writing, so here are a few tips on keeping up to date with the Node:

If you don’t want to miss a single post, the easiest thing to do is sign up for our e-mail alerts. They currently go out once a day if there was at least one new post that day. If you are a registered user of the Node, you can also change your e-mail settings to only receive certain categories. For example, if you just want to read news and no interviews, or only want meeting reports and don’t care about career posts, you can customize all that, so you’re  only sent the information that you’re interested in.

Another way to read the Node is by RSS. Not everyone we talked to knows how to use this, so here’s a brief explanation: RSS feeds are a useful way to keep track of sites that update regularly, such as blogs or scientific journals or news websites. (The best explanation of RSS is probably this video). Websites that have an RSS feed will usually have a little icon like the one pictured here somewhere on the site, or next to the url in your browser’s address bar. To read RSS feeds, you need a feed reader. Google has one that’s free to use from within your web browser (so you don’t need to download anything). It works a bit like an e-mail program: every time you visit your feed reader, you’ll see which websites have updated since you last looked. Most journals use RSS feeds as well, and the four table of contents that we show in the Node sidebar to the right are in fact the RSS feeds of these journals. If you follow a lot of regularly updated websites (journals, blogs, the Node, news websites) and don’t want their updates to clutter your e-mail inbox, give it a try! The Node has feeds for some subsections of the site as well as a feed for everything, so you can pick what you want to read from our RSS page.

Finally, you can of course still visit the Node website the old fashioned way. In fact, you’re getting a lot more out of it if you do! You can see the list of events, use the links in the sidebar, see the journal table of contents, read people’s comments, and if you feel like it, you can leave a comment yourself: Anyone can comment on the Node, even without an account, but we do ask that you fill out your e-mail address. Leaving your e-mail address is just a safety measure to prevent abuse of the comment feature, and the address is not displayed on the site.

If you have any other questions about reading the Node, let us know, either in the comments or via e-mail.

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Here are the research highlights from the new issue of Development…

TORc1-ing about stem cell differentiation

In adult tissues, the tight regulation of stem cell selfrenewal and differentiation maintains tissue homeostasis. In Drosophila ovaries, BMP signalling from the local environment maintains germline stem cells (GSCs) by repressing bam (a differentiation-promoting gene) expression. Now, on p. 2461, Rongwen Xi and co-workers reveal a role for the tumour suppressor tuberous sclerosis complex proteins, TSC1/2, in GSC maintenance. Human TSC1 and TSC2 proteins form a complex that negatively regulates TOR, a conserved kinase involved in cell growth. TOR functions mainly via the TORC1 complex, which activates the protein translation initiator S6K. Disruption of Tsc1 or Tsc2 in Drosophila GSCs, the researchers report, leads to precocious GSC differentiation and loss. Elimination of S6K rescues this phenotype, which implicates TORC1 hyperactivation in the precocious differentiation of Tsc1/2 mutant GSCs. TORC1 hyperactivation also negatively regulates BMP signalling. Thus, suggest the researchers, TSC1/2-TORC1 signalling maintains Drosophila GSCs by controlling both BMP-Bam-dependent and -independent differentiation programs, a role that might be conserved in mammals.

Olfactory neuronal precursors sniffed out

Neuronal precursors in the developing olfactory epithelium (OE) produce olfactory receptor, vomeronasal and gonadotropinreleasing hormone neurons, neuronal classes that are essential for chemosensation, social interactions and reproduction. Now, Anthony-Samuel LaMantia and colleagues characterise two distinct populations of neuronal precursors in the mouse OE that give rise to these neuronal types (see p. 2471). They describe a population of slowly dividing, self-renewing precursors mainly in the lateral OE that express high levels of Meis transcription factors and a population of rapidly dividing neurogenic precursors mainly in the medial OE that express high levels of the Sox2 and Ascl1 transcription factors. The Meis dose in the first population reduces Ascl1 expression and neurogenesis, they report, whereas the Sox2 dose in the second population, which is partly controlled by local Fgf8 signalling, promotes OE neurogenesis by suppressing Meis1 and enhancing Ascl1 expression. These insights into the characteristics of OE neuronal precursors should facilitate the identification of the adult OE neural stem cells that generate olfactory receptor and vomeronasal neurons throughout life.

Ringing the changes on bivalent gene silencing

In pluripotent ES cells, key developmental regulators contain ‘bivalent chromatin domains’ – regions that carry epigenetic markers of both repressed and active chromatin, and that assemble RNA polymerase (RNAP) complexes. Thus, these bivalent domains silence genes, but keep them primed for timely activation and are thought to resolve into repressed or active domains upon ES cell differentiation. But are bivalent chromatin domains involved in in vivo development? On p. 2483, Véronique Azuara and colleagues report that these domains operate in the early mouse embryo. They show that several somatic lineage regulators (including Hox factors) retain bivalent chromatin domains in cells that are committed to the extra-embryonic lineage. However, these genes, in contrast to similar genes in pluripotent cells, are not engaged by the Polycomb repressive complex component Ring1B. Instead, these bivalent genes are selectively targeted for Suv39h1-mediated repression through H3K9 methylation, and for RNAP exclusion upon trophoblast lineage commitment. Thus, Ring1B and Suv39h1 play mutually exclusive roles in the establishment of distinct chromatin states during early mouse lineage commitment.

On PAR1 spindle orientation promotes neurogenesis

In the developing vertebrate CNS, ‘deep’ cells differentiate into neurons whereas undifferentiated superficial epithelial cells continue to proliferate. The rate of neuronal differentiation depends on the balance between these two cell types, which are generated by asymmetric divisions of the superficial cells. Now, Jeremy Green and co-workers reveal that the conserved polarity protein PAR-1 promotes these asymmetric divisions in the neural plate of Xenopus embryos by controlling spindle orientation (see p. 2501). PAR-1, which is basolaterally localised in epithelia, is required for the differentiation of deep cells. By grafting marked superficial cells that express activated PAR-1 onto untreated embryos, the researchers show that PAR-1 drives the generation of deep cells from the superficial epithelium. Depletion experiments indicate that PAR-1 is normally required for vertically orientating epithelial mitotic spindles, thereby ensuring a sufficient number of asymmetric cleavages. Importantly, the effect of PAR-1 on spindle orientation not only generates deep cells, note the researchers, but also promotes neurogenesis by partitioning these cells away from anti-neurogenic, apically localised atypical protein kinase C.

Ectodermin damps down Nodal

During early vertebrate embryogenesis, gradients of the TGFβ-related factor Nodal control embryonic pluripotency and establish the body plan. But how do embryonic cells interpret subtle changes in Nodal signalling? According to Stefano Piccolo and colleagues, the negative intracellular Smad regulator ectodermin (Ecto) determines how mouse embryonic cells read Nodal signals in vivo (see p. 2571). Recent results suggest that the ubiquitin ligase ectodermin acts as an intracellular regulator of TGFβ signalling by monoubiquitylating Smad4, which causes the disassembly of the R-Smad/Smad4 transcriptional complex that mediates TGFβ signalling. Here, the researchers show that ablation of Ecto in trophoblast cells disrupts the balance between stem cell self-renewal and differentiation by increasing their Nodal responsiveness, a result that reveals a new role for Nodal signalling in trophoblast development. In the epiblast, they report, Ecto deficiency shifts mesoderm fates towards node/organiser fates. These and other results suggest that the negative control of Smad activity by ectodermin orchestrates early mouse development by ‘tuning’ the responses of extra-embryonic and embryonic cells to Nodal.

Polycomb recruitment to DNA: Spps enlisted

Polycomb group (PcG) protein complexes repress gene expression during the development of higher eukaryotes by binding to Polycomb group response elements (PREs). Little is known about how PcG complexes are recruited to PREs but, on p. 2597, Lesley Brown and Judith Kassis suggest that Spps (Sp1-like factor for Pairing Sensitivesilencing) might be involved in this process in Drosophila. All known Drosophila PREs contain binding sites for Sp1/KLF zinc-finger proteins. The researchers now report that the Sp1/KLF family member Spps binds to Ubx and engrailed PREs, and to polytene chromosomes in a binding pattern that closely matches that of the PcG protein Psc. Spps deletion suppresses ‘pairing-sensitive silencing’, they report, a PRE-associated activity in which somatic-chromosome pairing increases PcG-mediated repression. Spps mutation also enhances the phenotype of pho mutants; the PcG protein Pho is involved in, but not sufficient for, PcG complex recruitment to PREs. Together, these results suggest that Spps works with, or in parallel to, Pho to recruit PcG complexes to PREs.

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