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In Development this Week (Vol. 144, Issue 13)

Posted by , on 4 July 2017

Here are the highlights from the current issue of Development:

 

Heart tube formation: a gut reaction

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Morphogenesis of the endoderm-derived foregut (FG) is tightly linked to that of the mesoderm-derived heart tube (HT), with both structures arising at approximately the same time and place in the developing embryo. However, the physical forces that create the FG and HT are unclear. Here, Larry Taber and colleagues combine experimental approaches in chick embryos with computational modelling to explore this issue (p. 2381). They propose that differential anisotropic growth between the mesoderm and endoderm drives tissue folding and formation of the FG while also bringing the bilateral heart fields (HFs) into close proximity. Indeed, inhibition of cell proliferation (using the mitotic inhibitor Aphidicolin) together with computational simulations confirm that proliferation is required for this initial step. They further propose that actomyosin contraction in the anterior intestinal portal (AIP; the caudal opening of the FG) then generates tension that elongates the FG and the fused HFs. In line with this, inhibition of contraction (using the myosin inhibitor blebbistatin) and modelling analyses reveal that contraction is required for FG and HF elongation. Finally, the authors reveal that the fused HFs thicken and expand – driven by an accumulation of cardiac jelly – to eventually create the HT. Together, these findings highlight a new model that integrates HT and FG morphogenesis.

 

mTORC-ing some sense into pancreas development

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In recent years, much progress has been made in uncovering the signalling pathways and transcriptional networks that can influence pancreas development during embryogenesis. However, comparatively little is known about postnatal development of the pancreas, and whether nutrients can impact pancreas development and function after birth. Now, James Wells, Katie Sinagoga and colleagues demonstrate that the nutrient-sensing mTOR pathway regulates the maturation and function of mouse pancreatic islets postnatally (p. 2402). They first reveal that mTOR is dispensable for embryonic development but is required for normal postnatal islet development, with levels of mTOR signalling being highest in the first few weeks after birth. The researchers further report that deletion of mTOR in the endocrine pancreas causes a decrease in islet mass and compromised islet maturation and morphogenesis; this is accompanied by a decrease in islet function. Finally, the authors show that the two known mTOR-containing complexes – mTORC1 and mTORC2 – mediate distinct functions of mTOR: while mTORC1 predominantly regulates islet maturation and function, mTORC2 influences islet mass and morphogenesis. Overall, these findings highlight a potential role for nutrient-sensing mechanisms during postnatal islet development and maturation, a finding that has important implications for deriving functional β-cells in vitro.

 

A role for cell repulsion during placental labyrinth formation

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The placental labyrinth – a complex structure made up of trophoblasts and endothelial cells – provides the interface for gas and nutrient exchange between the embryo and the mother and hence is essential for embryogenesis. However, the molecular mechanisms that underlie the development of this vital labyrinth, particularly those that influence its vascularization, are poorly understood. Here, on p. 2392, Yoshiaki Kubota, Satoru Yamagishi and co-workers report the unexpected finding that fibronectin leucine-rich transmembrane protein 2 (FLRT2), which is a protein that acts as a chemorepellent in neurons, regulates placental labyrinth development in mice. They report that FLRT2 is expressed in endothelial cells specifically in the placental labyrinth. The researchers further demonstrate that the vasculature is poorly formed and aberrantly organized in FLRT2-deficient placentas, with FLRT2-deficient embryos exhibiting high levels of hypoxia. In vitro assays reveal that, as occurs in neurons, FLRT2 signals through UNC5B and can mediate cell repulsion. Following on from this, the authors show that Unc5b deletion recapitulates the vascular defects observed in Flrt2-deficient placentas. Together these exciting results point towards a role for inter-endothelial repulsion, mediated by FLRT2, during placental morphogenesis.

 

PLUS…

 

An interview with Bill Harris

Embedded ImageWilliam ‘Bill’ Harris is Head of the Department of Physiology, Development and Neuroscience at the University of Cambridge, UK, and a Fellow of both the Royal Society and Academy of Medical Sciences. His lab works on the development of the vertebrate nervous system, with a particular focus on cell lineage in the retina. In 2017 he was awarded the British Society for Developmental Biology’s Waddington Medal for outstanding research performance and services to the community. We met Bill in his Cambridge lab to talk science, art and ice hockey. Read the Spotlight on p. 2307

 

 

MicroRNAs in neural development: from master regulators to fine-tuners

The proper formation and function of neuronal networks is required for cognition and behavior. Indeed, pathophysiological states that disrupt neuronal networks can lead to neurodevelopmental disorders such as autism, schizophrenia or intellectual disability. In recent years, it has been shown that microRNAs (miRNAs), an abundant class of small regulatory RNAs, can regulate neuronal circuit development, maturation and function by controlling, for example, local mRNA translation.  Here, Marek Rajman and Gerhard Schratt provide an overview of the most prominent regulatory miRNAs that control neural development, highlighting how they act as ‘master regulators’ or ‘fine-tuners’ of gene expression, depending on context. See the Review on p. 2310

 

Human haematopoietic stem cell development: from the embryo to the dish

Haematopoietic stem cells (HSCs) emerge during embryogenesis and give rise to the adult haematopoietic system. Understanding how early haematopoietic development occurs is of fundamental importance for basic biology and also for recapitulating the development of HSCs from pluripotent stem cells in vitro. Here, Alexander Medvinsky and colleagues discuss what is known of human haematopoietic development: the anatomical sites at which it occurs, the different temporal waves of haematopoiesis, the emergence of the first HSCs and the signalling landscape of the haematopoietic niche. They also discuss the extent to which in vitro differentiation of human pluripotent stem cells recapitulates bona fide human developmental haematopoiesis, and outline some future directions in the field. See the Review on p. 2323

 

 

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A day in the life of a modern Lernaean Hydra…

Posted by , on 3 July 2017

I am Eleni Chrysostomou, a PhD student in Uri Frank‘s lab at the National University of Ireland, Galway. The Frank lab’s general interest is development and regeneration, stem and germ cell biology, neural fate commitment, and the chromatin biology underlying these processes. The focus of my project is the roles of SoxB transcription factors (TFs) during nervous system development and regeneration. More specifically, my hypothesis is that SoxB TFs are expressed sequentially in the neural lineage and play a role in neural progenitor cells (NPCs) migration from the body column to the site of injury to re-establish and regenerate the missing head region. The work is mostly done in an in vivo context utilizing transgenic animals, as well as various molecular techniques.

According to the Greek mythology, one of Hercules’ labours was to kill the sea monster Lernaean hydra. What he didn’t know was that every time he decapitated one of the monster’s heads, it would grow back in triplicate! But how is that even remotely related to stem cell biology…

With that said, meet our animal model Hydractinia. Hydractinia, a marine colonial hydrozoan can be described as a great representative of the Cnidaria phylum and an excellent animal model to study cell and developmental biology, as its utility let to the assembly of the very first concepts and terms in biology, including the characterization of stem cells (Weismann, 1883).

The stem cells founded in Hydractinia (aka interstitial cells: i-cells) remain collectively pluripotent throughout the organism’s life and they express germ line markers such as Nanos, Vasa and Piwi (Bradshaw et al., 2015; Plickert et al., 2012). Hydractinia can be easily cultured and genetically manipulated in the laboratory without any ethical restrictions, and its application is suitable in various disciplines.

Hydractinia has a relatively simple life cycle. Following fertilization, the embryonic development lasts 36-48 hours and upon induced metamorphosis the primary polyp is asexually reproduced to give rise to the new colony (Figure 1). The resulting members of an individual colony share a gastrovascular space, nervous system and migratory stem cells by maintaining tissue continuity (Gahan et al., 2016)

 

Figure 1: The life cycle of Hydractinia (Image obtained from Flici et al., 2017, Cell Reports).

 

What really makes this animal so intriguing is its regenerative abilities. Like the mythical creature Lernaea, upon decapitation the animal is able to regenerate a fully functional and complete head just within three days (Figure 2).

 

Figure 2: Live imaging of head regeneration in Hydractinia (Image obtained from Bradshaw et al., 2015, eLife).

 

What do we do with our “non-mainstream” animal model…

The Frank Lab is based in the National University of Ireland Galway and it is composed of post-graduate students and Post-docs with each of us exploring a different aspect of the biology of these animals in order to answer fundamental questions spanning from developmental biology to epigenetics.

Some of the projects that are currently running in our lab are: whole body regeneration from small tissue fragments (Hakima Flici – Post-Doc), the role of Piwi genes in development and regeneration (Emma McMahon – PhD student), histone variants in Hydractinia (Anna Torok – PhD student), sexual commitment (Timothy Dubuc – Post-Doc).

A typical day in our lab is anything but ordinary.  We start the day by spawning the animals and collect the embryos for injection. As the time window for injection is quite narrow – only half an hour before they start dividing – you don’t have much of a choice but to wake up and run downstairs to the manipulation room. After the running and once injection is done, you can breathe for a bit but not for long. The animals need to be fed after all that effort given to the spawning. Generally, there is not much time to lay back and enjoy a nice cup of coffee – not a tea person – but we still love it (that’s why we are in research I guess). Once the feeding is done, you can go back to the lab and see what’s the plan for the day and continue with the experiments that you left from last night – most of the protocols have overnight incubations or you were just too tired and hungry to keep working, lets be honest. And before you realize it it’s already late in the afternoon! The working hours in Ireland can be a bit tricky during the summer time (not really summer, but oh well) as the day light can last until 10-11 o’clock in the night and you have no sense of the actual time! The supervisors are happy during that period…

Even though working with a not so popular animal model can be a bit demanding, it gives us the opportunity to study developmental aspects not feasible in other animal models. Although structurally simple, Hydractinia encompasses a complex gene repertoire that is highly conserved to their sister branch bilaterians.  Not many organisms are able to regenerate body parts and especially their heads. This pioneering model for stem cell biology gives as a highly valuable advantage to gain insights on why other animals including humans have limited or zero abilities to regenerate missing parts of their bodies.

 

The Frank Lab. Some people missing as we never manage to get a picture with all of us.

 

 

References

Bradshaw, B., Thompson, K., Frank, U. (2015) Distinct mechanisms underlie oral vs aboral regeneration in the cnidarian Hydractinia echinata. Elife, 4:e05506.

Flici, H., Schnitzler, C.E., Millane, R.C., Govinden, G., Houlihan, A., Boomkamp, S.D., Shen, S., Baxevanis, A.D., Frank, U. (2017) An evolutionarily conserved SoxB-Hdac2 crosstalk regulates neurogenesis in a Cnidarian. Cell Rep, 18: 1395-1409.

Plickert, G., Frank, U., Muller, W.A. (2012) Hydractinia, a pioneering model for stem cell biology and reprogramming somatic cells in pluripotency. Int J Dev Biol, 56:519-534.

Weismann, A. (1883). The origin of the sexual cells in hydromedusae. Jena. Gustav Fischer

Gahan, J.M., Bradshaw, B., Flici, H., Frank, U. (2016) The interstitial stem cells in Hydractinia and their role in regeneration. Curr Op Gen & Dev, 40:65-73.

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PhD Position in Vertebrate Neurodevelopment and Evolution

Posted by , on 3 July 2017

Closing Date: 15 March 2021

A fully funded PhD position is available in the Laboratory of Regulatory Evolution (Tschopp group) at the Zoological Institute, University of Basel, Switzerland.
Our research interests focus on two main questions: How is phenotypic diversity generated during vertebrate embryogenesis? And how can developmental processes be modified to drive morphological evolution?
The present project will investigate the potential for developmental plasticity in the limb neuromuscular system in response to changes in dactyly, i.e. altering digit numbers. Specific questions we will address include: How are muscle patterning and motorneuron axonal pathfinding coping with changes in digit numbers in vertebrate hands and feet? How is motorneuron pool complexity in the spinal cord affected by additional digit targets in the periphery? We will use a range of methods, including experimental embryology in chicken, genetic mouse models, axonal backfilling, NextGeneration-Sequencing and functional experiments using gene knock-down and overexpression.
The project builds on solid foundations of confirmed preliminary data. For more information please visit http://evolution.unibas.ch/tschopp/research/index.htm
The successful candidate will have a Master (or equivalent) in developmental biology and/or molecular biology, and ideally will have skills in experimental embryology, neurobiology and NextGeneration-Sequencing. A basic understanding of Unix and the R language for statistical computing would be beneficial.
Please send your application with a brief statement of motivation, CV and contact(s) for references (where applicable) to patrick.tschopp@unibas.ch
Evaluation will begin mid-August 2017 and suitable candidates will be contacted shortly after – earliest starting date is Sept. 1st 2017.

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PhD student positions in sponge and coral EcoEvoDevo

Posted by , on 3 July 2017

Closing Date: 15 March 2021

Multiple PhD opportunities in EcoEvoDevo of sponges and corals are available at the Research School of Biology, Australian National University. The projects are related to regeneration, biomineralization, evolution of developmental gene regulatory networks and microbiomes, see http://biology.anu.edu.au/research/labs/adamska-lab-genomic-and-evolutionary-basis-animal-development for details. All projects provide exciting and varied research experience by combining cell and molecular biology approaches with bioinformatics and field work in temperate and tropical marine environments. The students will be based in the Adamska lab at the ANU, and will be involved in local, national and international collaborations. The successful candidates will commence the doctoral program in late 2017 or early 2018.

The positions come with substantial research and travel budgets, and the candidates are encouraged to apply for scholarships to fund personal living expenses. The ANU is administering domestic and international PhD scholarships ($26,682 per annum for a period of 3 years with a possibility of a 6-month extension). Scholarship application deadlines are 31st of August (international applicants) and 31st of October (domestic applicants).  Queries regarding scholarship matters can be directed to rsb.studentadmin@anu.edu.au. Shortlisted candidates will receive support in preparing the scholarship applications, with a possibility of internal funding for “near miss” applicants.

Interested candidates should contact Maja Adamska maja.adamska@anu.edu.au by July 31st 2017, providing current CV, 500-1000 words description of research interest including preference for one or more of the listed projects, and contact details for two academic references.

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Postdoc position in evo-devo at Sars Centre, Bergen

Posted by , on 26 June 2017

Closing Date: 15 March 2021

A 3-year postdoc position is available in the group of Dr. Patrick Steinmetz at the Sars Centre in Bergen (Norway) to study the evolution of animal nutrient and growth homeostasis .

The project is based on a tissue-specific transcriptome analysis comparing fed and fasting animals in the sea anemone Nematostella vectensis. The successful applicant will be involved in further validating some of the resulting signalling, neuronal or growth control genes and studying their functional role in nutrient and growth homeostasis. With that aim, the applicant will use and further develop state-of-the-art functional techniques (CRISPR, transgenesis) and combine those with a diverse range of physiological, imaging and molecular biology techniques available.

Further details on the application, position and contact details can be found here: https://t.co/RFzeVLAG9J

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Postdoctoral Position in Cardiovascular Development

Posted by , on 23 June 2017

Closing Date: 15 March 2021

A postdoctoral position is available in the laboratory of Dr. Sophie Astrof at Thomas Jefferson University to study roles of cell-extracellular matrix interactions during cardiovascular development and disease. My laboratory utilizes genetics, cell biology and confocal imaging to elucidate developmental and molecular mechanisms of aortic arch artery patterning and the formation of the cardiac outflow tract. These processes are essential for neonatal viability, and defects in the formation and remodeling of the outflow tract vasculature underlie common and severe forms of human congenital defects. Experience with genetic manipulation, embryology and cell biology is desirable. My laboratory is a part of a modern and well-equipped Center for Translational Medicine at Jefferson Medical College (http://www.jefferson.edu/university/research/researcher/researcher-faculty/astrof-laboratory.html) located in the heart of Philadelphia. To apply, send a letter of interest, CV and names and contact information of three references to sophie.astrof@gmail.com

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Postdoctoral position, Developmental Genetics, University of Colorado Anschutz Medical Campus

Posted by , on 22 June 2017

Closing Date: 15 March 2021

A postdoctoral position is immediately available at the University of Colorado Anschutz Medical Campus in Aurora, Colorado in David Clouthier’s lab to study molecular mechanisms regulating facial morphogenesis. The laboratory is currently investigating the molecular and cellular functions of basic helix-loop-helix transcription factors and non-coding RNAs in facial development, with an emphasis on understanding the regulatory landscape influenced by these factors and RNAs. This includes CRISPR/Cas9 model generation in mice and zebrafish. In addition, a systems biology approach is being taken to model early gene expression within the developing pharyngeal arches of mouse and zebrafish embryos in an attempt to create an in silico developmental program. Finally, new mutant mouse models being developed by KOMP2 are being screened in order to find novel genes regulating craniofacial and cardiovascular development. We use a combination of modern genetic approaches in both the mouse and zebrafish to address these topics.

Applicants should have a Ph.D. or M.D./Ph.D. and a strong background in developmental biology. Experience with mouse genetics and/or zebrafish embryology is a plus. Salary support will be based on the current NIH pay scale. In addition, individuals will be encouraged and supported to submit fellowship applications as part of an overall mentoring program. Please send a cover letter of your research interests and past research experience, CV and contact information for three references to Dr. David Clouthier (david.clouthier@ucdenver.edu).

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Postdoctoral position, Genetics and Development of Morphological Evolution, University of Oklahoma

Posted by , on 21 June 2017

Closing Date: 15 March 2021

A postdoctoral position is available in J.P. Masly’s lab at the University of Oklahoma (www.maslylab.com) to study the genetic, developmental, and evolutionary bases of morphological variation among Drosophila species. Our research focuses on understanding how evolutionary change at the genetic level directs variation in development that gives rise to species-specific phenotypic differences.

The successful candidate will have a Ph.D., and will also have a strong background and research interests in evolutionary biology, developmental biology, and genetics. Candidates with experience in Drosophila genetics and molecular biology are particularly encouraged to apply. The initial appointment will be made for one year, with a possible extension up to three years. Salary will be commensurate with experience and the start date is flexible.

To apply, visit https://jobs.ou.edu and submit the following materials for job position number 171344:

— A cover letter explaining why you would like to join the lab group and a statement of research interests
— Curriculum vitae, including a list of publications
— Contact details for two or three academic referees

Informal inquiries are welcome and should be sent to J.P. Masly (masly[at]ou.edu). For additional information visit http://www.maslylab.com/Opportunities.html.

The position is available immediately and will remain open until filled.

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Woods Hole images 2015, Round 2 – The winner

Posted by , on 21 June 2017

The votes are in for our latest Development cover competition with entries from the 2015 class of the Woods Hole Embryology Course. 

With 333 votes counted, we have a winner:

4th Place (13% of the votes) – Drosophila

3rd Place (25% of the votes) – Skate

2nd Place (26% of the votes) – Parhyale

1st Place (36% of the votes) – Crab

 

 

This cute crab was collected from a plankton tow Chiara Sinigaglia
 from the Observatoire Océanologique de Villefranche sur Mer/ CNRS, France. Congratulations Chiara! And thanks to our other entrants Amjad Askary, Longhua Guo, Maike Getwan, Nick Shikuma and Elena Boer.

Look out for another round in the coming weeks.

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Photo Contest

Posted by , on 21 June 2017

Hello everyone!! My name is Nadia Edelsztein and I am a PhD student from Argentina working in the Reproductive and Development field!

I am addressing you all to ask for a big favour. I entered a photo contest a couple of weeks ago, held by the institute where I used to learn German. The idea was to show pictures that, somehow, made you see things differently or from a different perspective. I chose a photo of one of the control immunohistochemistry assays I have done during my PhD project. It is an epididymis section from a 9dpp mouse that got all curled up during mounting but still looks beautiful -to me, at least. I have entitled it “Neben” (,,Nebenhoden” is epididymis in German). Even though I do not compete for the big prizes, I am in the run for “people’s choice award” and it is the only picture related to Science. You can only vote once and through Facebook.

So…I would like to ask you all if you could vote for my photo and, if you wish to do so, share the link with friends, acquaintances, etc! I am posting my pic at the end of this message for you to see which one is it.

In order to vote, you will have to click the following link and a website will open (it is in Spanish, so I apologise for that). There, you have to click on my photo (if you want to do so…please want to do so!!) and the little circle next to it turns black. Then go to the bottom of the page and click on the green button that says “Enviar” (which means “send” in Spanish). After that, there will be something displayed on a new page (all in Spanish) saying something very similar to “Thank you for participating! The winners will be announced July 5th, etc”.

 

Link to vote: https://goetheinstitut.fbapp.io/b…/WAK8n5LzZRRA6LQzrwRNqbop…

 

Thank you all for taking the time to read this!! Thanks to The Node for allowing me to share this!! And I apologise for the long post!!

 

Here is Neben (isn’t it beautiful? ♥):

 

 

Cheers!!

Nadia

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