Turtles are peculiar vertebrates. They have a compact skull with no temporal openings, a beak instead of teeth, a contractible neck, and a shell covering its trunk. The famous turtle shell is composed of two halves, a plastron (ventral) and a carapace (dorsal). The latter is an exquisite arrangement of vertebrae and fan-shaped ribs with secondary ossification forming a rib cage that encloses the limb girdles.

Side view of a turtle skeleton. Illustration by M A Smith.

Please, take a moment to imagine your shoulder inside your rib cage. How such intriguing anatomy has evolved from a standard external-to-the-ribs configuration? As drastic as this change may seem, researchers from the Japanese RIKEN Center for Developmental Biology provided an elegant and straightforward explanation.

Scapula (sc) position and ribs (r) in birds and turtles. Modified from Figure 2 of Kuratani et al. (2011) [1].

A basic step for evolutionary studies is to understand the history of the group. Who is it related to? The evolutionary relationships of turtles within the amniotes (mammals, reptiles, and birds) are not well understood. The traditional view based on skull morphology places them as basal reptiles while more recent molecular data group them with birds and crocodilians. A robust phylogenetic hypothesis allow us to infer evolutionary processes by the arrangements of nodes and characters. However, it is generally difficult to extract more fine-grained insight about how the changes occurred. Fossils do provide direct evidence of ancient forms, but they are rare. Can we do better?

A turtle hatchling. Photo by Mayer Richard.

“All that we call phylogeny is today, and ever has been, ontogeny itself. (…) Phylogeny is but a name for the lineal sequences of ontogeny, viewed from the historical standpoint.” (Whitman, 1919; via Hall 1999)

Embryonic development is the process that builds the morphology of multicellular organisms. Scrutinizing development help us understand how structures are formed and regulated during ontogeny, and thus, how variant patterns can arise. Comparing the developmental sequence of a structure in different organisms may provide insightful information about evolutionary changes and the origins of morphological characters; given that you have a working phylogenetic hypothesis and a certain amount of care, since development also evolves.

To investigate the developmental changes related to the turtle unique body pattern Nagashima et al. (2009) [2] did exactly this: followed the developmental sequence of the turtle Pelodiscus sinensis while comparing to the correspondent stages in chicken and mouse embryos. This comparative approach allowed to pinpoint the exact moment in time when the morphology of the embryos began to differ during development and correlate the data with adult body patterns. And what they saw was simply awesome.

The authors observed that the scapula appeared lateral to the body wall, near the limb bud (see above, ribs: white; scapula: green), and with similar muscular connections in the three embryos. The ribs of the turtle embryo were shorter in length while the ribs of the mouse and chicken had grown ventrally into the lateral body wall. At this stage, except for minor positional differences and rib length, the musculoskeletal pattern of the embryos was quite similar. But from this point on the turtle embryo began to differ from the other two.

In the mouse and chicken embryos the scapula simply grows posteriorly, above the ribs. Instead, in P. sinensis the scapula does not grow a posterior blade-like portion and is held inwards by a lateral folding of the body wall. It is positioned over the first rib and is encapsulated by the second rib which grows laterally and anteriorly. The trunk muscles connecting the scapula to the back retained their ancestral connections only adjusting to the “new” position. Limb muscles, on the other hand, formed new connections that are turtle-specific.

The process is much easier to understand with 3D animated embryos:

Movies provided by the Laboratory for Evolutionary Morphology, RIKEN Center for Developmental Biology and available here.

It is interesting to note that rib development is somehow refrained from moving ventrally and the ribs remain in the axial region (unlike other amniotes whose ribs grow ventrally). This might inhibit the posterior growth of the pectoral girdle and is possibly the reason why ribs grow laterally in the turtle. This lateral growth and the body wall folding enclose the limb girdles.

Chicken (left) and turtle (right) ribs (arrows) positioned ventrally and laterally, respectively. Image by Shigeru Kuratani.

What could be regulating these ontogenetic movements? Right above the folding of the body wall there is a thickened ectoderm with undifferentiated mesenchyme forming a longitudinal ridge which is unique to turtles. This Carapacial Ridge (CR) is coextensive with rib growth and shares histological and molecular characteristics with the Apical Ectodermal Ridge, responsible for the patterning of limb buds. For these reasons it is believed to have a role in the turtle shell formation, although its functions remain unclear. Implanting CR grafts more dorsally or ablating the ridge did not alter rib growth, although in the latter the tips of the ribs joined distally at the site of the wound. These experiments suggest that the CR does not induce rib growth, but may regulate the fan-shaped pattern of the ribs.

Carapacial Ridge of the turtle P. sinensis (arrowheads indicate the lateral of the embryo, where the longitudinal ridge begins). Modified from Figure 1 of Nagashima et al. (2007) [3]

The development of a modern turtle does not reconstitute the evolutionary history of its kinds, but it can provide clues to the underlying mechanisms of the turtle body evolution. For instance, if the CR indeed is responsible for the maintenance of the fan-shape pattern of the ribs, it is likely that ancient turtles with fan-shaped ribs had a CR during embryonic development. It is also possible to make predictions based on the observed developmental processes; for example, that the arrest in rib growth preceded the enclosure of the scapula during evolution. Ribs encasing the lateral body wall ventrally would pose a physical barrier to the displacement of the scapula, so it is more likely that rib growth was altered first.

Fact checking these predictions is complicated and we must rely on fossils to get a glimpse of the past.

Before 2008 the oldest known turtle fossil was Proganochelys, a creature that had a complete shell and internal girdles. Since it already had a turtle body pattern, not much information could be extracted to understand the onset of the group’s evolution. But in 2008, Li et al. [4] found a 220 million years old fossil of an ancient turtle with many interesting (read intermediate) features, named Odontochelys.

What does it looks like? It had a plastron, but not a carapace; its ribs were not fan-shaped, but were short and not bended ventrally; and the scapulae are ahead (rostral) of the ribs, but not underneath. It also had teeth and many other specific anatomical details.

Illustration of Odontochelys by Marlene Donnelly.

Not only Odontochelys morphology is compatible with Nagashima et al. (2009) observations, but the shoulder anatomy even roughly paralels an early stage of P. sinensis development, although muscle connections were not clear. The authors speculate that the CR of Odontochelys was reduced and did not form a complete carapacial margin because the ribs do not exhibit a fan-shape pattern and there is no carapace.

Odontochelys could be interpreted as an intermediate stage for the turtle shell evolution, unless, of course, the apparent absence of a carapace is the result of a secondary reduction. Reisz & Head (2008) [5] argue that some modern turtles have greatly reduced the ossification of dermal components of the carapace, commonly associated to aquatic environments. Truncation of the carapace ossification is a plausible developmental mechanism that would lead to Odontochelys morphology. And the debates go on…

Anyway, developmental and fossil evidence insinuate that the once thought dramatic body pattern transformation, might well have occurred by a series of gradual developmental changes during turtle evolution. Nagashima and colleagues also made an animation about their take on the turtle evolution:

Laboratory for Evolutionary Morphology, RIKEN Center for Developmental Biology

Things I wonder: how large is the variation of scapular positioning pattern within the turtles? Does their ecological habits influence shoulder anatomy? Does the secondary loss of the carapace (leatherback) affect girdle positioning?

Literature

1. Kuratani, S., Kuraku, S., & Nagashima, H. (2011). Evolutionary developmental perspective for the origin of turtles: the folding theory for the shell based on the developmental nature of the carapacial ridge Evolution & Development, 13 (1), 1-14 DOI: 10.1111/j.1525-142X.2010.00451.x

2. Nagashima, H., Sugahara, F., Takechi, M., Ericsson, R., Kawashima-Ohya, Y., Narita, Y., & Kuratani, S. (2009). Evolution of the Turtle Body Plan by the Folding and Creation of New Muscle Connections Science, 325 (5937), 193-196 DOI: 10.1126/science.1173826

3. Nagashima, H., Kuraku, S., Uchida, K., Ohya, Y., Narita, Y., & Kuratani, S. (2007). On the carapacial ridge in turtle embryos: its developmental origin, function and the chelonian body plan Development, 134 (12), 2219-2226 DOI: 10.1242/dev.002618

4. Li, C., Wu, X., Rieppel, O., Wang, L., & Zhao, L. (2008). An ancestral turtle from the Late Triassic of southwestern China Nature, 456 (7221), 497-501 DOI: 10.1038/nature07533

5. Reisz, R., & Head, J. (2008). Palaeontology: Turtle origins out to sea Nature, 456 (7221), 450-451 DOI: 10.1038/456450a

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Over the past months, we’ve heard from several people who left research for a career away from the bench. Now, a summary of all these posts appears in Development, followed by some tips for graduate students, postdocs, and their supervisors. Below is the full text of the article, but it’s also free on Development, and you can get it as a PDF from there.

Leaving the lab: career development for developmental biologists

Let’s face it: not all PhD students and postdocs will become lab heads. Every few years, the National Science Foundation surveys doctorate recipients in the USA about their career progression, and their latest published data (collected in 2006) show that only about one quarter of biomedical science PhDs held tenured or tenure-track positions (see the links at the bottom of this post). If graduate and postdoctoral training are merely apprenticeships for tenure-track jobs, these numbers suggest that there are too many people being trained for the number of research jobs that are available. But if trainee positions are more than a stepping stone to running a research lab, what value does a PhD in the life sciences have outside of the lab, and what types of job do the remaining three quarters of PhD graduates go on to have?

In July 2010, I asked the following questions on the Node: `Should there be fewer postdoc and PhD positions? Or different kinds of [research] trainee positions, where some include training for scientific careers outside of the lab?’

The ensuing discussion suggested that the PhD degree and the postdoc system are not in need of reform, but that attitudes towards these positions should change. Greg Dressler, a professor at the University of Michigan, wrote in a comment on the Node post, `I do think we need to get over the idea that nothing short of an academic career fulfills the ideal goal of our students and post-docs. Most of the folks I went to graduate school with are not in academia anymore, yet they have meaningful and successful careers.’ In the same discussion, James Briscoe, a group leader at the MRC National Institute for Medical Research suggested that we need `the acknowledgment and encouragement of a diversity of career routes and development paths’.

These are good suggestions. There are a number of jobs outside of research or academia that are suitable for PhD graduates. A research job in industry, for example, connects seamlessly to research experience gained during PhD and postdoctoral training. But not every PhD graduate wants to continue in a research career, academic or otherwise. What kind of non-research jobs are available and how do PhD graduates get these jobs? And how is scientific training useful to people in a non-research career? To answer these questions, I invited a number of people to write a post on the Node to explain how they moved away from a career in research after their PhD. These posts can be found on the Node, but it’s worth discussing here the trends they raise collectively, and distilling some of the advice from those people who have left the life of the lab bench behind them.
(more…)

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Here are the research highlights form the current issue of Development:

Modelling liver development with ES cells: HNF4A is key

Human embryonic stem cells (hESCs), via their ability to differentiate into a plethora of cell types, offer an attractive approach for regenerative medicine, but they also offer a means of studying cell differentiation, and hence development, ex vivo. Here, Stephen Duncan and co-workers analyse the differentiation of hESCs to probe the molecular mechanisms that underlie human hepatocyte differentiation (see p. 4143). Using a protocol in which hESCs differentiate into hepatocytes in a stepwise manner, the researchers show that each stage of the differentiation process is associated with a characteristic mRNA profile, as shown by microarrays. Importantly, they show that the transcription factor HNF4A, which has been implicated in liver development, is essential for specifying hepatic progenitors; the onset of HNF4A expression is associated with specification of the hepatic lineage from hESCs, and shRNA-mediated knockdown of HNF4A prevents hESC differentiation into hepatic progenitors. These and other studies demonstrate that HNF4A establishes the expression of a network of transcription factors that promote hepatocyte cell fate.

Gcm/Glide-ing to a glial fate

Neurons and glia originate from a common precursor, the neural stem cell (NSC). These multipotent precursors display a high degree of plasticity in vitro, but the basis of this plasticity and the mechanisms underlying the neuron-glial switch in vivo are unclear. Now, Angela Giangrande and colleagues (see p. 4167) show that the transcription factor Glial cells missing (Gcm, also called Glial cell deficient; Glide) triggers a conserved chromatin signature that converts Drosophila NSCs to a glial fate. The researchers show that overexpression of Gcm in fly NSCs produces glia at the expense of neurons. This gliogenic potential of Gcm decreases with time and does not affect quiescent NSCs, suggesting that it is dependent on temporal cues rather than on the mitotic potential of NSCs. Finally, the investigators demonstrate that the glial fate switch is associated with a chromatin signature, which includes low levels of histone H3 lysine 9 acetylation and is similar to that observed in vertebrate glia, suggesting that this epigenetic mechanism for specifying glia has been conserved throughout evolution.

Paired up: histone methylation and HP1γ

The pairing of chromosomes during meiosis requires histone modifications, such as histone H3 lysine 9 di- and tri-methylation (H3K9me2 and H3K9me3, respectively), at pericentric heterochromatin (PCH) regions. But how do these epigenetic marks control chromosome interactions? Haruhiko Koseki and colleagues demonstrate that heterochromatin protein 1γ (HP1γ) regulates chromosome interactions by recognising histone methylation marks during meiosis in mice (see p. 4207). The researchers show that, in meiotic spermatocytes, H3K9me2 by the G9a histone methyltransferase requires pre-existing H3K9me3 marks, which are deposited by the Suv39h histone methyltransferase. They further show that HP1γ recognizes H3K9me3 marks and localises to PCH regions in an H3K9me3-dependent manner, where it then recruits G9a. Importantly, the loss of HP1γ results in defective spermatogenesis, aberrant centromere clustering and impaired homologous chromosome pairing. The authors thus propose that HP1γ acts as an important link between the cascade of H3K9me3 and H3K9me2 modifications, acting to align homologous chromosomes and facilitate their pairing during meiosis.

A new look into Sfrps and Wnt

Secreted frizzled-related proteins (Sfrps) are classified as Wnt antagonists, but recent studies have shown that some Sfrps can positively modulate Wnt signalling. Is this a general property of all Sfrps and, if so, how do Sfrps regulate Wnt signalling? Here, Paola Bovolenta and colleagues (see p. 4179) show that Sfrp1 and Sfrp2 positively regulate Wnt signalling, and are required for Wnt-mediated development of the mouse optic cup. The researchers show that specification of the peripheral optic cup (OCP), which is known to be dependent on Wnt signalling, is grossly defective in mice lacking both Sfrp1 and Sfrp2. In these mutants, Wnt spreading across the OCP is impaired, suggesting that Sfrps can influence the diffusion of Wnts. In support of this, the researchers demonstrate that Sfrp1 overexpression flattens the gradient of Wingless (a Drosophila Wnt homologue) across the Drosophila imaginal disc. These studies highlight a new and unexpected role for Sfrps in regulating the levels and distribution of Wnts during development.

Kidney development: a Notch above the Wnts

The kidney comprises functional units known as nephrons, which are made up of specialised epithelial cells. During development, each nephron arises from a pool of stem cells that undergo mesenchymal-to-epithelial transition (MET) in response to signals such as Wnt4 and Wnt9b. Here, Raphael Kopan and co-workers show that Notch pathway activation can replace inductive Wnt signals during this process (see p. 4245). Using gene manipulation in cultured kidneys, the researchers show that Notch pathway activation can induce epithelialisation in nephron stem cells but not in the closely related stromal mesenchymal cells. Continued Notch pathway activation following MET directs cells towards a proximal tubule fate. Finally, they report, Notch-induced MET can occur in the absence of Wnt4 and Wnt9b, suggesting that nephron stem cells are poised to undergo MET, which requires a permissive signal that can be provided by Wnts or by Notch pathway activation. These studies shed new light on our understanding of the early cell fate decisions that are made during kidney development.

Ngn2 phosphorylation links neurogenesis to the cell cycle

Cell cycle length influences the balance between progenitor maintenance and differentiation in the nervous system, although the mechanism for this is unknown. Here, Anna Philpott and co-workers show that multi-site phosphorylation of neurogenin 2 (Ngn2), a master regulator of neuronal development, controls neuronal differentiation in response to cell cycle lengthening in Xenopus embryos and in mammalian P19 cells (see p. 4267). The researchers show that, in Xenopus extracts, Ngn2 phosphorylation is regulated by the cell cycle, and analyses of HeLa cell extracts show that Ngn2 is phosphorylated on multiple sites by cyclin-dependent kinases (cdks). The phosphorylation of Ngn2, they report, reduces its ability to induce neuronal differentiation in vivo, and this is due to the decreased ability of phosphorylated Ngn2 to bind to its target promoters. The authors thus propose a model in which multi-site phosphorylation of Ngn2, which is quantitatively sensitive to cell cycle length, is used as a way to interpret cdk levels in order to control neuronal differentiation in response to cell cycle lengthening during development.

Plus…

The control of developmental phase transitions in plants

Plant development progresses through distinct phases, each controlled by genetic pathways that integrate endogenous and environmental cues. Recent studies, reviewed by Huijser and Schmid, show that the genetic networks underlying the transitions between these phases share some common factors.

See the Review article on p. 4117

Modeling new conceptual interpretations of development

As reviewed by Julien Vermot and Markus Affolter, the EMBO workshop on Biophysical Mechanisms of Development (organized by Ana Borges, Ana Certal, Ana Tavares, Filipa Alves and Beatriz Garcia Fernandez) brought together scientists in the field of developmental biology for whom interdisciplinary and quantitative approaches are central to the issues they are investigating.

See the Meeting Review, p. 4111

(1 votes)
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Applications are invited for a Principal Investigator position to lead a new research group in Cell and Developmental Biology. We are particularly interested in candidates using quantitative approaches to study any aspect of the cellular and molecular dynamics of developing tissues.

Candidates should have an outstanding track record and an ability to lead a team pursuing original long-term research goals. Core support, including laboratory and animal staff will be provided by the Medical Research Council. MRC-NIMR offers an exciting, supportive and collaborative environment, comprising state-of-the-art imaging and mass spectrometry, high throughput sequencing and computational facilities, FACS, and excellent transgenic fish, frog, mouse and Drosophila facilities

For an overview of research at NIMR, see www.nimr.mrc.ac.uk

Informal enquiries to J-P Vincent (jvincen@nimr.mrc.ac.uk) or James Briscoe (jbrisco@nimr.mrc.ac.uk)

Applications should include a cover letter, full Curriculum Vitae, the names and addresses of three referees, an outline of current research interests (1 page) and a proposal for future research (1-2 pages).

The level of appointment will be determined based on expertise and experience. Benefits include Membership of MRC Final Pension Scheme and 30 days annual leave.

Closing date: 31 October 2011 Interview date: to be confirmed

Applications are handled by the RCUK Shared Services Centre; to apply please visit our job board at https://ext.ssc.rcuk.ac.uk and complete an online application form. Applicants who would like to receive this advert in an alternative format (e.g. large print, Braille, audio or hard copy), or who are unable to apply online should contact us by telephone on 01793 867003, Please quote reference number IRC 27831.

The MRC is an Equal Opportunities Employer
Final appointments will be subject to a pre employment screening

(1 votes)

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Survey
As you know we carried out a survey about the Node this summer. Thank you to those who answered our questions! It was very helpful. We’re currently analysing the results, and you can expect a report on the Node soon.
One lucky survey participant, Greg Shanower of The Commonwealth Medical College in Scranton, Philadelphia (US), won the prize draw, and has been sent some gifts from Development and the Node. Congratulations!

Technical updates
We’ve been battling some technical glitches on the Node. At the moment, commenting is not working properly. We’re trying to find a solution for this as soon as possible. We may need to take the site down for a short while later this month to work on this and general site updates, but will let you know about that beforehand. You can always find us on Facebook and Twitter to keep up to date on any site downtime or to leave us comments, or you can email us directly via thenode[at]biologists.com .

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Thanks to the support from the Company of Biologists I had the opportunity to attend the 70^th SDB meeting that was held last month in the hot but wonderful city of Chicago. During three days we enjoyed more than 60 excellent talks and about 500 really good posters that were focused on different aspects of developmental biology …

We had the opportunity to hear many outstanding talks but two of them particularly caught my attention, the one given by Tom Kornberg during the Presidential Symposium and the one given by Peter Reddien during the Stem Cell Biology Session. Tom Kornberg lectured us about the specificity of a long distance signalling mechanism that operates during Drosophila imaginal discs development and involves the use of cytonemes, specific types of filopodia that work as channels through which  morphogen signalling proteins move from a producing cell to a target cell.  Peter Reddien gave a remarkable talk about the molecular basis of regeneration in planarians, in which he explained to us how a single transplanted neoblast (adult planarian stem cell) can restore the regenerative capacity of a lethal irradiated worm.

Among the sections I enjoyed the most was the Hilde Mangold Posdoctoral Symposium where eight SDB postdoctoral members gave short talks that were judged by a committee who selected the best speaker to receive an Award. The winner of this year was Lena Ho from the Institute of Medical Biology in Singapore.

During the closing session we had the pleasure of listening to the Awards lectures where Gail Martin and Ruth Lehmann gave two extraordinary talks in which they made a summary of their successful scientific careers.

The meeting was exceptionally well organized, everything from the welcome talk to the Closing banquet went perfectly.

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We’re as surprised as you are that September starts in a few days! Time to get a new desktop calendar.

While it may look like an African violet, this is actually a staining of the four-cell stage of a slipper limpet (Crepidula fornicata) just about to cleave to the eight-cell stage. This image, taken by Anna Franz of the University of Oxford, was one of the candidates in the second Development cover image voting round of images taken at the 2010 Woods Hole Embryology course.

Visit the calendar page to select the resolution you need for your screen. The page will be updated at the end of each month with a new image, and all images are chosen from either the intersection image contest or from the images we’ve featured from the Woods Hole Embryology 2010 course.

(3 votes)

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During the European summer Edinburgh, the Scottish capital, is famously the place to be at while it hosts its world-renowned Festival. But this year it is also the place where the European Zebrafish Meeting was celebrated. The efforts of the Local and International Organizing Committees of the 7^th European Zebrafish Meeting made this possible.

As a 2nd year PhD student, I was very keen to visit this exciting city and to take part in my first international meeting. The opening reception consisted of a cocktail in the Edinburgh International Conference Centre, which gave visiting researchers the chance to meet fellow scientists from other countries but also to have a look at the sponsors’ stands. It was a promising start that was then followed by four days of amazing talks and poster sessions.

The attendees had the opportunity to choose from a wide variety of sessions on subjects such as behavior, sensory systems, regeneration and stem cells, infection and immunity, organogenesis, muscle, skin and connective tissue, cancer and, of course, development. All of those I managed to attend had excellent speakers. In particular, I enjoyed Robert Reinhardt’s (Wittbrodt Lab) talk about vertebrate synexpression genes, where he showed that synexpression groups (composed of spatio-temporally co-expressed genes which act in the same biological process) share common cis-regulatory motifs. As my own project is on eye development I was also partial to the talk by Fabienne Poulain (University of Utah) who proposed a model to explain the trajectory of retinal axons in the optic tract. She explained how dorsal axons in the retina arrive to the lateral part of the tectum and how the others degenerate. This sorting is a heparan sulfate-dependent mechanism.

Florence Marlow´s talk (Solnika-Krezel lab) about the new cell polarity pathway component Gpr125 was also very interesting. This gene is involved in the stabilization of polarity within the plane of an epithelium. Finally, it’s certainly worth mentioning Florencia Cavodeassi´s talk (Stephen Wilson lab) about morphogenesis of the forebrain. She explained the important role that boundaries of Ephrin activity in the anterior neural plate have in the specification of the eye field and the subsequent morphogenesis of the forebrain.

During the poster sessions, students like myself shared our research and got helpful feedback from doubts with the wide variety of experts available, who were happy to discuss our queries.

At this meeting, PhD students like me had a great opportunity to expand our scientific knowledge. It doesn´t matter what you are working on, at the EZM you can learn a lot about what people are doing all over the world and about the latest techniques available. Hopefully, you can also discover new tools that might be useful for your own project and which you had not considered.

Once the talks had finished, the hosting committee organized a concert in St. Mary’s Cathedral, where we enjoyed listening to one of the most famous choirs in the world.

However, this was not the end of our cultural experience. We were yet to see the most emblematic place in Edinburgh. The visit to Edinburgh Castle during the last night of the Meeting was amazing.  The environment transported us back to the Middle Ages. We could breathe the power of many Scottish kings. We were treated to a cocktail in the courtyard, where we enjoyed a performance by a group of bagpipers: you have not experienced Scotland if you’ve not heard bagpipes.  It was all very exciting indeed.

Finally, Berta Alsina and the Spanish committee presented a brief overview of Barcelona (Spain) where the next European Zebrafish Meeting will take place in 2013.

If, like myself, you have fish as your experimental model, I encourage you to attend a zebrafish meeting at some point during your PhD because it opens up the possibilities of what your model can do for you, and you get to meet many people from the community. The Edinburgh Meeting was a great occasion to learn about cutting edge science and I am very glad I was part of it.

Enjoy the photos and feel free to share your comments.

(4 votes)

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The Cell: An Image Library

Help us reach our goal of 1000 members in our LinkedIn group. Join us at http://www.linkedin.com/groups?about=&gid=3733425.

The Cell: An Image Library http://www.cellimagelibrary.org

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Here are the research highlights from the current issue of Development:

Shaping up the Hippo pathway

The Hippo pathway, which regulates cell proliferation, is regulated by cell density: low cell density induces weak Hippo signalling, leading to nuclear accumulation of the transcriptional co-activator Yap and the promotion of proliferation, whereas high cell density prevents nuclear accumulation of Yap and suppresses proliferation. The mechanisms by which cells detect density, however, are unknown. Here, on p. 3907, Hiroshi Sasaki and colleagues show that cell morphology plays a key role in regulating the Hippo pathway. The researchers show that manipulation of NIH3T3 cell morphology, by culture on fabricated microdomains, regulates the subcellular localisation of Yap. These changes in cell morphology, they report, lead to changes in actin stress fiber quantities and the subsequent regulation of Yap phosphorylation and localisation. Finally, the researchers show that stress fibers regulate Yap upstream of, or at the level of, the protein kinase Lats. The researchers thus propose that a cell morphology-based mechanism, mediated by stress fibers, cooperates with a cell adhesion-based mechanism to achieve density-dependent control of cell proliferation.

Vreteno: a novel protein in germline piRNA biogenesis

In Drosophila, Piwi-interacting RNAs (piRNAs) preserve genome integrity in the germline by silencing mobile genetic elements, such as transposons. On p. 4039, Ruth Lehmann and co-workers report the identification of Vreteno, a novel gonad-specific protein that is essential for germline development and primary piRNA biogenesis in Drosophila. The researchers demonstrate that vreteno (vret), which was identified in a screen for maternal-effect mutations affecting oocyte polarity, is essential for germline development. They further show that Vret, which contains two Tudor domains, interacts with Piwi and Aubergine to regulate their stability and subcellular localisation. Using microarray analyses, they confirm that vret regulates transposon silencing in both the germline and somatic tissues of the Drosophila gonad. Finally, the authors report, in the absence of Vret, Piwi-bound piRNAs are lost, whereas piRNAs can engage in Aubergine- and Argonaute 3-dependent `ping-pong’ amplification. The authors thus suggest that Vreteno regulates transposon silencing by acting at the early stages of primary piRNA processing.

Joining forces: PCP and apical-basal polarity

Cell polarity can be defined in terms of the polarity of a cell with respect to others in the same plane (planar cell polarity; PCP), or in terms of polarity based on the subcellular localisation of cell structures, proteins or domains (apical-basal polarity; ABP). The extent to which these polarity pathways are linked, however, is unclear. Here, Janet Heasman and colleagues investigate interactions between the PCP protein Vangl2 and the ABP component aPKC in Xenopus oocytes (p. 3989). The researchers show that Vangl2 is enriched animally in subcortical islands, where it interacts with vesicle associated membrane protein 1 (VAMP1) and acetylated microtubules. The distribution of these islands and the microtubule cytoskeleton, they report, is dependent on aPKC. Importantly, the researchers show that both maternal Vangl2 and aPKC are required to establish asymmetries in the oocyte and early embryo. These data highlight important links between the PCP and ABP pathways, suggesting that Vangl2 and aPKC are part of a common network that influences oocyte and embryo patterning.

Snail enhancers step out of the shade

The expression of critical developmental genes can be regulated by multiple cis-regulatory modules (CRMs), and it has been suggested that remote CRMs are redundant to promoter proximal CRMs. But what is the function of these multiple CRMs and are they truly redundant? To answer this question, Angelike Stathopoulos and co-workers (p. 4075) examine two CRMs from the Drosophila snail gene locus and show that these CRMs interact in a non-additive manner to regulate snail expression. The researchers demonstrate that the CRMs drive distinct patterns of gene expression in early embryos. Furthermore, they report, the distal CRM acts to limit the expanded expression domain of the proximal CRM, whereas the proximal CRM serves to `dampen’ the levels of expression driven by the distal CRM. Importantly, the CRMs are not functionally equivalent; only the distal CRM is required in snail transgenes to rescue snail mutants. Thus, the authors propose, complex interactions between CRMs are required for fine-tuning the patterns and levels of snail expression during development.

Ciliogenesis: arrested development at the node

The rotation of cilia on cells within the node of mammalian embryos generates a leftward fluid flow that establishes left-right asymmetry. But what regulates ciliogenesis at the node? Here (p. 3915), Yuji Mishina and colleagues show that cell cycle arrest, mediated by bone morphogenetic protein (BMP) signalling, is required in node cells to trigger nodal ciliogenesis in mice. The authors show that epiblast-specific deletion of Acvr1, which encodes a BMP type 1 receptor, results in abnormal left-right patterning in early embryos; the node forms in these mutants but nodal ciliogenesis is compromised. Using Acvr1-deficient mouse embryonic fibroblasts, they further demonstrate that BMP signalling through ACVR1 positively regulates p27^Kip1 stability and phosphorylation, which in turn maintains quiescence and allows the formation of primary cilia. Importantly, the researchers report, p27^Kip1 is present and phosphorylated in quiescent nodal cells, whereas the corresponding cells in Acvr1 mutants are proliferative and show reduced p27^Kip1 expression and phosphorylation. These studies provide valuable insight into the mechanisms by which primary cilia form at the node.

Distinct roles for Nodal and Cripto in stem cells

Extra-embryonic endoderm stem (XEN) cells can be derived from the mouse primitive endoderm, which gives rise to two extra-embryonic tissues: the visceral endoderm (VE) and the parietal endoderm. However, despite displaying many characteristics of primitive endoderm, XEN cells only contribute effectively to parietal endoderm in mouse chimeras. Here, Michael Shen and co-workers study the differentiation of XEN cells in response to Nodal, a member of the TGFβ superfamily, and Cripto, a Nodal co-receptor (p. 3885). Importantly, the researchers show that XEN cells treated with either Nodal or Cripto display an up-regulation of VE markers and contribute to VE in chimeric embryos. Notably, they report, the response of XEN cells to Nodal and Cripto differs: the response to Nodal is blocked by treatment with an Alk4/Alk5/Alk7 kinase inhibitor, whereas the response to Cripto is unaffected, suggesting that Cripto can act independently of these receptors’ activity. These findings provide key insights into visceral endoderm specification and define distinct pathways for Nodal and Cripto during cell differentiation.

Plus…

Mechanisms of thymus organogenesis and morphogenesis

The thymic microenvironment supports T cell development and regeneration and, as reviewed by Gordon and Manley, recent studies have made significant progress in identifying the mechanisms that control the specification, early organogenesis and morphogenesis of the thymus. See the Review article on p. 3865

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