Here are the highlights from the current issue of Development:

One-step transdifferentiation

Terminally differentiated cells are generally considered to be in a developmentally locked state in vivo; they are incapable of being directly reprogrammed into an entirely different state. Now, on p. 4844, Joel Rothman and co-workers show that the expression of a single transcription factor can trigger the transdifferentiation of fully differentiated, highly specialised cells in C. elegans larvae and adults. They show that brief ectopic expression of ELT-7, a GATA transcription factor that regulates intestinal differentiation, can specifically convert non-endodermal cells of the pharynx into fully differentiated intestinal cells. This conversion is accompanied by an increase in the expression of intestine-specific genes and a concomitant decrease in the expression of pharynx-specific markers and structural proteins. The reprogrammed cells also exhibit morphological characteristics of intestinal cells. These, together with other findings in the study, demonstrate that terminally differentiated cells can be reprogrammed to an alternative fate without the need for cell division, without the requirement for a dedifferentiated intermediate state and without prior removal of an inhibitory factor.

Stem cells and regeneration in a new light

Zebrafish have a remarkable capacity to regenerate and, as such, are being used increasingly to study stem cells and organ regeneration. Here, Chen-Hui Chen, Kenneth Poss and colleagues establish a luciferase-based approach for visualising stem cells and regeneration in adult zebrafish (p. 4988). The researchers generate several transgenic lines that enable ubiquitous or tissue-specific expression of both firefly luciferase and mCherry. They show that, unlike the fluorescence signal, bioluminescence in these lines, which they term zebraflash, readily penetrates through adult tissues and can easily be detected. Using the cardiac zebraflash line, they demonstrate that this approach can be used to monitor the extent of heart injury and subsequent regeneration in animals in a non-invasive and high-throughput manner. Furthermore, they report, this approach can be used to detect quantitatively the progeny of engrafted stem cells in recipient animals at high spatial resolution. This methodology, along with the transgenic lines presented here, offer a valuable resource for the study of stem cells and regeneration.

Rocking the Wnt pathway

Wnt signalling plays important roles during embryonic patterning and in tissue homeostasis, and mutations that affect the Wnt pathway are associated with cancer. Despite this, the exact way in which the Wnt pathway is regulated is still not fully understood. Now, Amy Bejsovec and colleagues uncover a novel regulator of Wnt signalling (p. 4937). Previous studies have shown that the Drosophila RhoGEF Pebble (Pbl) might influence patterning mediated by Wingless (Wg), the primary fly Wnt. Following this, the authors show that both loss- and gain-of-function Drosophila pbl mutants exhibit defects that are consistent with a role for Pbl in negatively regulating the Wg pathway. Furthermore, both Pbl and ECT2, the human homologue of Pbl, downregulate Wnt reporter activity in cultured Drosophila and human cells, highlighting a role for ECT2 as a potential proto-oncogene. Finally, the researchers show that, unlike most negative regulators of the Wnt pathway, Pbl acts downstream of Armadillo/β-catenin and may act through Rho1 to negatively regulate Wnt/Wg signalling.

Opening a passage for hair growth

The hair follicle epithelium forms a tube-like structure that is continuous with the epidermis, but how the lumen of this structure is created during morphogenesis and regeneration remains unclear. Now, Sunny Wong and colleagues identify a novel population of cells that initiates hair follicle lumen formation in mice (p. 4870). The researchers first provide a detailed characterisation of the infundibulum, the region encompassing the hair follicle mouth, and identify a population of keratin 79 (K79)-positive epithelial cells within this region. Using lineage tracing, they show that these cells are specified early during hair follicle development and migrate outwards from the hair germ into the epidermis prior to lumen formation. This migratory event is also observed during regeneration of the hair follicle; K79-positive cells are specified in the secondary hair germ and migrate out, eventually forming a continuous layer with pre-existing K79-positive cells. These findings identify both a novel mode of epithelial tube morphogenesis and a unique population of cells that migrate throughout the life cycle of the hair follicle.

Insm1 controls pituitary endocrine cell development

The pituitary gland is an endocrine organ that plays a role in various physiological processes, including growth, metabolism and reproduction. The development of various pituitary endocrine cells is influenced by a number of transcription factors and signals. In this issue (p. 4947), Carmen Birchmeier and colleagues report that the transcription factor Insm1 controls the differentiation of all endocrine cells in the mouse pituitary. The researchers show that Insm1 is expressed in pituitary progenitors and continues to be expressed in differentiated endocrine cells. Using Insm1 knockout mice, they demonstrate that Insm1 controls a pan-endocrine differentiation programme; genes encoding pituitary hormones or proteins involved in hormone production and secretion are downregulated in Insm1 mutant pituitary glands. By contrast, Notch signalling components and skeletal muscle-specific genes are upregulated, suggesting that Insm1 also represses inappropriate gene expression programmes in the pituitary. Finally, the researchers show that the SNAG domain of Insm1 is required for its function, acting to recruit histone-modifying proteins and transcriptional regulators.

Split thoughts on the neural crest

The neural crest (NC) is a transient structure that gives rise to multiple lineages. Despite intense studies, it is still unclear whether the NC represents a homogeneous population of cells. Here, Jean Paul Thiery and colleagues examine this issue (p. 4890). The authors first characterise the cranial neural fold in chick and mouse embryos and show that, prior to delamination, it contains two phenotypically distinct domains: neural ectoderm and non-neural ectoderm. The researchers then show that the two domains display temporally distinct delamination patterns. Cells specifically within the non-neural ectoderm are the first to delaminate, whereas a second population of delaminating cells then originates from the neural ectoderm in both chick and mouse embryos. Importantly, they report, cells within the two domains have distinct fates: those from the non-neural ectoderm give rise to ectomesenchymal derivatives, whereas those within the neural ectoderm give rise to neuronal derivatives. These, together with other findings, prompt the authors to revisit current definitions of the NC and the origin of ectomesenchyme.

PLUS…

Mechanisms of scaling in pattern formation

Many organisms and their constituent tissues and organs vary substantially in size but differ little in morphology; they appear to be scaled versions of a common template or pattern. Here, David Umulis and Hans Othmer investigate the underlying principles needed for understanding the mechanisms that can produce scale invariance in spatial pattern formation and discuss examples of systems that scale during development. See the Review article on p. 4830

Conveying principles of embryonic development by metaphors from daily life

How can the revolution in our understanding of embryonic development and stem cells be conveyed to the general public? Here, Ben-Zion Shilo presents a photographic approach to highlight scientific concepts of pattern formation using metaphors from daily life, displaying pairs of images of embryonic development and the corresponding human analogy. See the Spotlight article on p. 4827

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Meeting report for Genetics Otago symposium 28-29^th November 2013.

The annual Genetics Otago symposium was held in the newly refurbished HD Skinner Annex of the Otago Museum in sunny (yes, really!) Dunedin, New Zealand at the end of November.   This two-day symposium is run annually by Genetics Otago, a Research Centre of the University of Otago, which has over 240 members based at Otago and right across New Zealand. This year the meeting brought together plenary, guest and postgraduate speakers from Otago and across NZ, in addition to invited speakers from overseas (Australia, Czech Republic). Highlighting the diversity of genetics research, presentation topics ranged from the genomics of NZ stick insects, liver disease, gout, brain development, chordate evolution through to cancer genetics.  Below are a few highlights; for more details check out the Storify of the live tweeting from the symposium: http://storify.com/ANZSCDB/geneticsotago-symposium-2013.

Professor Vicky Cameron’s (Christchurch Heart Institute) group has been studying the genetics of susceptibility to Takotsubo cardiomyopathy or broken heart syndrome, cases of which increased following the two Christchurch earthquakes, especially in post-menopausal women. She and Professor Martin Kennedy, also of University of Otago Christchurch, are championing differing hypothesis for the genetic origin of this condition – a single, rare causative gene mutation versus a ‘perfect storm’ of contributing SNPs.

Dr Amy Osborne (Laboratory for Evolution and Development) spoke about her work identifying the mechanisms behind transgenerational inheritance and the predictive-adaptive response (“Are you what your great grandmother ate?”) where various behaviours or health conditions can be inherited without DNA sequence changes.  In work leading on from the PhD of Sarah Morgan, Dr Osborne has been making use of Drosophila to investigate nutritionally derived transgenerational inheritance in the F3 population following feeding of the F0 generation on a restricted diet.

Sophia Cameron-Christie, a PhD student with Professor Stephen Robertson, presented on the genetics of biliary atresia, a developmental disorder of the bile duct, which is usually only treatable by liver transplants in children affected by this condition.  Sophia is using exome sequencing and linkage analysis on samples from a NZ family to identify susceptibility loci.  Two other PhD students from Professor Robertson’s group also presented their PhD work, Adam O’Neil on periventricular heterotopia and neuronal migration, and Emma Wade on mechanosensing and bone density.

Professor Neil Gemmell (Department of Anatomy) spoke on his work on the increasing evidence that the mitochondrial genome has an important impact on sperm fertility and function, through a phenomenon termed ‘Mother’s Curse’ – whereby incremental mutations can accrue of no selective disadvantage to the mother, but are detrimental to sperm performance, sperm having far fewer mitochondria and more intense energy requirements than oocytes.

Tess Sanders (a PhD student from Dr Christine Jasoni’s group) spoke on how the maternal environment affects foetal brain development. It is well established in humans and other mammals that if the mother is obese, there is a much higher risk of the child being obese.  Tessa is studying gene expression changes and axon guidance in the arcuate nucleus, the part of the brain that receives signals whether to eat or not to eat, and has found molecular evidence that gene expression in this part of the developing brain of the embryo alters depending upon the diet of the mother.

Dr Nic Waddell  (Centre for Medical Genomics, University of Queensland) gave a excellent talk updating us on the ICGC (International Cancer Genome Sequencing) initiative, in particular where they are at with the Australian focus of the project, whole genome sequence analysis of pancreatic cancer, which has a very high mortality rate in those afflicted.

Associate Professor Andrew Shelling from the University of Auckland spoke on the role of Foxl2, a transcription factor they identified as playing a role in premature ovarian failure in NZ families. In initially unrelated work, his group also found point mutations in FoxL2 in many granulosa cell tumors and are now carrying out knockdown and overexpression studies in cell lines to determine how Foxl2 acts to cause ovarian cancer, and comparing this to its misfunction in premature ovarian failure

We were very pleased to have the ANZSCDB support a postgraduate speaker prize and with 12 high quality student speakers it was a hard decision for the judges. In the end, the award was presented to Megan Leask, currently writing up her PhD with Associate Professor Peter Dearden, who investigated the molecular mechanisms behind phenotypic plasticity using the honeybee as a model – whereby dietary differences (i.e. the feeding or otherwise of royal jelly to larvae) drive the development of very different adult organisms (queens vs workers).  In the hive, worker bee ovaries are repressed due to the presence of a queen in the hive; in the absence of the queen, the worker ovaries become activated and they start to lay eggs.  Megan used microarray and RNA-seq, chromatin-immunopreciptation (for epigenetic marks) and drug inhibitor functional studies to understand the molecular changes that occur, both gene expression and chromatin organization, for ovary reactivation, and hence may give us a better idea of how this phenotypic plasticity works at the molecular level.    Sophia Cameron-Christie and Tess Sanders won the GeneticsOtago Speaker award.

This was the 5^th year for the Genetics Otago Annual Research Symposium, and it was again a big success.  It is becoming so popular that registrant numbers had to be capped this year, but given the strong interest from outside Otago, next year’s meeting will be extended, with more researchers from the North Island encouraged to attend.  Looking forward to it already!

—– Dr Megan Wilson, ANZSCDB New Zealand representative and Genetics Otago member; Developmental Biology Laboratory, Department of Anatomy, University of Otago.

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This month saw many interesting posts on the Node, in addition to several job and PhD studentship adverts in our jobs page. Here are some of the highlights!

Node series

Our two series continued at full steam this month:

– In our outreach series, the Cosy Science team presented their ongoing project of bringing science to the relaxed environment of the pub, while Worm Watch Lab is a citizen science project in which the public helps scientists study egg laying in C.elegans. The Biology Builders participated in our series by sharing their experience of organising a stand in a science festival, as well as suggesting an easy outreach activity involving ping-pong balls!

– In our ‘A day in the life’ series Stephen Freeman described a day in the life of a chick lab, while James Lloyd wrote about the mysteries of working with moss.

Research

– Atsushi Miyawaki and colleagues wrote about their recent paper in Development using Fucci technology to comparatively characterise endoreduplication and endomitosis.

– The Chicago Journal club is back  and their first post of this academic year was a Cell Stem Cell paper on the importance of cell sorting in spatial patterning.

– and Christele considered a recent paper assessing the role of dickkopf-1 (dkk1) in neural progenitors.

Meeting reports

– Megan attended ComBio, the largest annual life sciences conference in Australasia, and wrote about her highlights.

– Lauren and Ioanna reported from the UPMC/Curie Developmental Biology course 2013.

– the Node attended the first joint meeting of the French Society for Developmental Biology and for Genetics.

Also on the Node

– We interviewed cardiovascular developmental biologist and Development editor Benoit Bruneau.

– Olivier introduced Manteia, a database that allows the comparison of embryological, expression, molecular and etiological data from human, mouse, chicken and zebrafish simultaneously

– and the deadline for the next round of Company of Biologists Travelling Fellowships, to help cover the costs of visiting another lab, is fast approaching

 
Happy Reading!

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A four-year PhD position is available to combine computer modelling with experimental work investigating stem cell specification, activity, and cell migration in the development and maintenance of the vertebrate cornea.

Further details are available here:

http://tinyurl.com/pmxm2cy

The deadline for applications is 16th December.  Please feel free to contact Prof Martin Collinson (m.collinson@abdn.ac.uk) or Dr Silke Henkes (silkehenkes@gmail.com) to discuss the project further.

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What is the earliest Phylum of metazoans to possess what we would recognize as a nervous system?

Did earlier organisms have all the components of a nervous system in the absence of what we would recognize as neurons?

What is a neuron?

Did nervous systems evolve independently more than once?

Where were all the molecular tool boxes that define a nervous system harnessed from?

These and related questions will be discussed in a three-day international meeting to be held in Florida, May 13-15, 2014.

Participants include recognized experts in the phylogeny of lower metazoans, comparative biologists interested in the cell and neurobiology of the same groups, and molecular biologists interested in the evolution of processes and molecules that underlie nerve function.

Contributed papers are invited for both oral and poster sessions.

Travel awards are available for students.

For full details see our website at: http://efns2.whitney.ufl.edu/

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The 4th Annual UPMC / Curie International Course on Developmental Biology titled “From Stem Cells to Morphogenesis” took place in Paris during a 5-week period in September-October 2013. Participants included both Masters and PhD students coming from all over the world. Students from Brazil, Canada, Greece, Portugal, France, Germany, Spain, England, India, Russia and Italy gathered together to take part in this special course.

The course was comprised of two complementary components. The first part included the practical workshops on the development of different animal models including Drosophila, Mouse oocytes and embryos, Zebrafish, Xenopus, Chick and Nematode. The workshop took place at Université Pierre and Marie Curie (UPMC) every day (except Sunday) for three weeks. Professors and Assistant Professors from all over Paris directed us during a series of experiments aimed at exploring the different advantages of the model systems. We also had the opportunity to work together with prominent guest researchers from the Stowers Institute in Kansas and University College London (UCL). Throughout the workshop students were encouraged to ask questions and to discuss with the professors about the different techniques that can be used to study each model system. The high quality of our instructors combined with the availability of modern equipment at each bench and within the university provided appropriate conditions for us to acquire a thorough understanding of every model presented.

The practical workshop was followed by two weeks of scientific talks given by French and International speakers, and there was an option to only participate in this portion of the course. The conference took place at the Institut Curie, which is located in the historic and beautiful Latin Quarter of Paris. Professors and renowned researchers from institutions such as Harvard, Cambridge, the Stowers Institute, UCL, UPMC, Institute Pasteur and Institut Curie presented recent and often unpublished data spanning a variety of interesting topics in developmental biology in different model systems. Subjects ranged from planarian regeneration to Drosophila morphogenesis, and from regulation of cell cycle to embryonic stem cell biology. Each lecture was followed by an active panel discussion. We had the opportunity to ask the speakers, who are experts in their respective fields, questions about their subject and research. In addition, following the talks we had the chance to discuss with the speakers in a more informal way over coffee and biscuits about things like our own research and future careers. All of us would agree that this was a unique and beneficial opportunity.

Furthermore, students had the opportunity to present an article during the course chosen by the guest speaker and then to propose an experimental design for future research. The advantages of this exercise were bidirectional; we were able to present in front of the author of the article which gave us the opportunity to acquire constructive feedback and advance our scientific way of thinking. Likewise, the researchers benefited from the chance to listen to some new ideas and research proposals on their own work from a different perspective.

Overall, this course provided us with an excellent opportunity to broaden our knowledge and understanding of developmental biology in an ideal environment that promoted discussion, critical thinking and learning. We acquired many new theoretical as well as practical skills that will help develop our scientific careers. However the experience was not only academic. On a more personal level, we were exposured to not only to a different educational system, but also to new cultures. Lasting friendships were made between people all over the world. We were able to bond over our shared interests in developmental biology and in this way help to build a future network of young scientists. All in all this was an extremely rewarding experience.

Ioanna & Lauren

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If you’re interested in how science is done, what it takes to make major discoveries, and how we got to where we are today, you may be interested in a book that’s just been published by Cold Spring Harbor Laboratory Press. The book’s called Blue Skies and Bench Space: Adventures in Cancer Research, and its proud and slightly-embarrassed-to-be-promoting-it author is me.

Modern biology was in its infancy when the Imperial Cancer Research Fund opened the laboratories in Lincoln’s Inn Fields which still exist today as the Cancer Research UK London Research Institute. Thanks to a succession of visionary Directors, who recruited a collection of fantastic scientists, the new labs rapidly became a byword for the ambitious, cutting edge work that its present occupants are still engaged in. However, half a century on, molecular biology and its offshoots are just part of the collection of weaponry in the multi-disciplinary research armoury we now have at our disposal, and the LRI is moving into a new phase of life, as part of the Francis Crick Institute. Blue Skies and Bench Space was written to ensure that the pioneering work that went on there is not forgotten.

From the start, the book was not intended to be a conventional lab memoir, where much of the interest lies in trying to find pictures of oneself and one’s friends. Rather, it was intended to be readable; a collection of non-fiction, scientific short stories, where the people are as important as the discoveries. So, within its pages you will find the dragons and sharks who occupied the Fifth Floor of the ICRF in the 1970s, and who played a huge part in the eukaryotic molecular biology revolution whilst scrapping merrily amongst themselves; the travails of a very tall postdoc who took a job at the ICRF to fill a spare year, and ended up discovering p53; the many and wonderful doings of Clare Hall; the collision of the growth factor and oncogene fields as masterminded by a fresh-faced young PhD student and his party animal boss; why Paul Nurse is so bad at French and so good at science; the link between Morris Dancing and death; sex, and how to determine it; and finally, and particularly of interest to developmental biologists, how a mix of fish, frogs, and chickens can culminate in hedgehogs.

If you fancy a dip into history, the book is available from its publishers, Cold Spring Harbor Laboratory Press, or on Amazon. All royalties from book sales will go to Cancer Research UK. Additionally, Blue Skies and Bench Space is free to read online, where you’ll also find an accompanying blog, with some of the background material and photos that wouldn’t fit into the book itself. I hope very much that you’ll take a look; there’ll be something there that you’ll enjoy, I think.

*************

Kathy Weston used to be a proper scientist but is now a science writer and communicator. See Falling Off the Ladder: How Not to Succeed in Academia for an account of how this happened.

Image 1- Cover art courtesy of Joe Brock, NIMR PhotoGraphics

Image 2- Paul Nurse off for a game of footy in the 1980s

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The Node will temporarily shutdown tomorrow, Friday the 29th of November, from 10 a.m. to 12 p.m. (GMT). We hope to be up and running soon after!

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Research, write grants, publish papers, teach, manage staff, collaborate. And now engage the public?!

Most scientists have their hands full, and while public engagement sounds nice in the abstract, actually finding time to do it well can be a challenge. This is the beauty of citizen science: it’s not just outreach, it let’s you get data you couldn’t get any other way. Citizens are asked to help solve a real scientific problem, so researchers get data to advance their work and members of the public get to experience an aspect of current science. It can be a powerful form of outreach because it highlights the sometimes tedious and often addictive search for new knowledge that characterises real science.

My experience with citizen science started last year when the Medical Research Council solicited ideas for public engagement activities to be associated with the celebration of the MRC Centenary in 2013.

At the time, I was a postdoc in Bill Schafer’s lab at the MRC Lab of Molecular Biology in Cambridge working on automated methods for analysing the behaviour of the nematode worm C. elegans. It was important that the analysis was automated because we had the equivalent of a four-month worm movie that had been collected over the previous couple of years using eight tracking microscopes (the movie has a cast of about 12 000 worms from over 300 mutant strains). When it came to analysing worm postures and locomotion, we were doing pretty well, but there are other behaviours that are more challenging to train computers to see. Here’s a close-up view recorded by Robyn Branicky:
 
 

 
Studying the genetics of egg laying in worms has shed light on a whole host of conserved pathways and we wanted to find more. There we were, with hours and hours of videos of worms doing their thing, including laying eggs, but it was just too much for one person to go through it all manually. Fortunately, even in our tracking videos, the only training you need to identify egg laying events is to watch a couple of examples. When the MRC asked for outreach project ideas, we figured we had a perfect match.
 
The result was Worm Watch Lab.
 
From the start we were working with the fine folks at Zooniverse on the project. This was an excellent experience and I can’t emphasise enough what a difference it makes to work with professionals who really know how to do citizen science. If we had tried to do this ourselves, even if we had hired professional developers to help with the site, there’s no way it would have gone as smoothly or resulted in such a nice finished product.

In addition to the basic function of watching videos and identifying egg laying events, it’s also possible for worm watchers to tag and comment on videos if they have a question or find something interesting. You can see the latest examples at http://talk.wormwatchlab.org/. This has let us see which aspects of the task people find challenging but it’s also been an opportunity for me to see things I assumed were in the data set but had never actually seen, like uncoordinated worms sitting in a huge pile of eggs or videos with larval worms that had already hatched (#tinyworms and #baby are popular tags).

Worm Watchers have classified an impressive 115 000 short video clips so far, but there’s still a lot more work to do (I estimate we’ll need to do about 1 million classifications to complete the task, but I can’t be more precise because we don’t yet know how many times each video needs to be viewed to ensure accurate classification).

If you want to see how citizen science can work in biology or if you’re just in the mood to watch some worm TV, please give us a hand (or at least a few mouse clicks!) and feel free to ask any questions on the talk page: http://talk.wormwatchlab.org/.
 
 
Andre Brown is a group leader at the MRC Clinical Sciences Centre at Imperial College London.
 

This post is part of a series on science outreach. You can read the introduction to the series here and read other posts in this series here.

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