You didn’t stop developing once you were born (or hatched).  Our infant selves barely resemble ourselves as adults, thankfully, and stem cells play an important role in this continued development.  A recent paper describes the identification of a stem cell niche that generates the melanophores that are responsible for the color patterning in adult zebrafish.

The color patterns that many animal species rely on for natural and sexual selection are generated by differences in melanin synthesis in melanophores.  During embryonic development, melanophores are derived from the neural crest.  In many species, such as zebrafish, the patterning seen in adults is established well after embryonic development—when the neural crest is no longer present.  A recent paper in Development describes the identification of melanophore stem cells that are inactive in the larval stages of zebrafish development, and later activated in juvenile zebrafish.  Dooley and colleagues found that the dorsal root ganglia serve as niches for these melanophore stem cells.  The melanophore stem cells are established early in embryonic development, and later spread out segmentally to produce the stripes seen on adult zebrafish.  These cells depend on the protein ErB for neural crest migration and the gene kit ligand (kitlga) to function as stem cells.  In the images above, recovering larval melanophores (green, arrowhead) migrate away from the position of the dorsal root ganglion (asterisk), along the spinal nerves, after morpholino knockdown of the transcription factor mitfa successfully depleted the existing larval melanophores.  The blue arrowhead points to a cell that later migrates.  This pattern resembles the proximity of melanophores to spinal nerves seen in wild-type juvenile zebrafish.

For a more general description of this image, see my imaging blog within EuroStemCell, the European stem cell portal.
Dooley, C., Mongera, A., Walderich, B., & Nusslein-Volhard, C. (2013). On the embryonic origin of adult melanophores: the role of ErbB and Kit signalling in establishing melanophore stem cells in zebrafish Development, 140 (5), 1003-1013 DOI: 10.1242/dev.087007

(7 votes)

Loading...

Regenerative Medicine: From Biology to Therapy

30 October-1 November 2013

Few topics in contemporary medicine have attracted more attention than stem cells and their potential for enabling the discovery of new regenerative therapies. The aim of this new Wellcome Trust Scientific Conference is to understand the biology that underpins the success or failure of regeneration, and to clarify the relationship between stem cell biology and regenerative biology so that both can be fully exploited to treat disease.

This meeting is aimed at scientists involved in developmental and regenerative biology, stem cell research, translational medicine, or clinical trials.

Scientific programme committee

Peter Coffey, UCSB, USA/ University College London, UK

Charles ffrench-Constant, University of Edinburgh, UK

Robin Franklin, University of Cambridge, UK

Topics will include:

• Regeneration biology: lessons from phylogeny

• Regeneration and therapeutics: the spectrum of regenerative efficiency in mammalian tissues

• Non stem cell-based regenerative biology

• Therapeutic regeneration by (stem) cell transplantation

• Reprogramming and transdifferentiation

• ES/iPS cell technologies

We welcome abstracts from all areas relevant to regenerative biology and regenerative medicine. Several oral presentations will be chosen from the abstracts submitted.

For more information, see: https://registration.hinxton.wellcome.ac.uk/display_info.asp?id=369

(1 votes)

Loading...

We are pleased to announce that an EMBO Workshop on Morphogen Gradients will be held in Lady Margaret Hall, Oxford, UK from 26 – 29th June 2013.

Registration is now open:

http://events.embo.org/13-morphogen/

The goal of this workshop is to bring together biologists, physicists and imaging specialists to discuss how morphogen gradients are generated and interpreted. After 20 years of molecular and genetic studies, the morphogen field has recently begun to use quantitative and biophysical approaches. These studies have led to surprisingly diverse findings and conclusions. For example, different modes of morphogen transport have been proposed and different ways of morphogen interpretation have been suggested.

The workshop aims to discuss the current status of the field and to seek input from other systems to stimulate new directions. Major emphasis will be placed on current debates in the field and the technical and theoretical developments that will address these issues. A broad range of speakers from both biological and physical sciences will ensure that the major systems and approaches in the field are covered.

In addition to the 21 invited speakers, an additional 10 speakers will be chosen from abstracts.

(3 votes)

Loading...

I recently came across a study by Milinkovitch and colleagues on the development of crocodile head scales. I think it highlights how nature sometimes chooses unusual ways to approach development, so I thought I would share a short summary here!

Scales, feathers and hairs are evolutionary adaptations to terrestrial life, fulfilling functions such as preventing water loss or protecting from UV radiation. It is unclear whether they are homologous structures or the result of convergent evolution, but all three structures are generated in a similar way. During embryogenesis, individual developmental units are genetically specified, each of them later forming, for example, an individual scale. The final surface organisation of these developmental units is thought to be established following a model first proposed by Turing over 60 years ago. According to this model, the local concentration of several chemical components, and the ability of cells to differentiate at unique thresholds of these components, generates different patterns.

A recent paper by Milinkovitch and colleagues, however, suggests that surface patterns may be determined using a different mechanism. By making 3D models of crocodile heads and mapping scale edges and nodes, the authors noticed how these scale patterns, unlike other reptiles, were not symmetrically organised in individual heads and were generally randomly distributed. Using these models, they analysed several features, such as edge angles and area distribution, concluding that the scales of the crocodile head are generated simply by physical cracking of the skin during development. This was evident during crocodile embryonic development: initially only major cracks are present, and these then branch and interconnect over time to form the final scale complexity.

Crocodile heads choose an alternative to the more common theme of genetic developmental determination of skin patterns, and it will be interesting to see whether a similar mechanism is used by other organisms (or body parts!). This work also shows how physical processes can be major players in certain developmental processes, an important reminder that genes do not always explain everything.

Milinkovitch MC., Manukyan L., Debry A., Di-Poi N., Martin S., Singh D., Lambert D., Zwicker M. (2013). Crocodile head scales are not developmental units but emerge from physical cracking, Science, 339 78-81

(4 votes)

Loading...

Did it ever occur to you that to enjoy music from Antonio Vivaldi to Lil Wayne, we use only about 22,000 sensory hair cells in our ears? Because hair cells are mechanosensors translating sounds to neural impulses, their irreversible degeneration causes hearing loss. Unlike amphibians and birds, we as mammals cannot spontaneously regenerate hair cells to restore hearing. This is in part why hearing loss is permanent. In order to identify hair cell progenitors in the postnatal cochlea, we took a pathway-centric approach and used active Wnt signaling (Axin2) as a marker. Much to our surprise, we detected robust Wnt activity in tympanic border cells, a poorly characterized group of cells directly beneath the organ of Corti (the hearing organ).

In this article, we show that Axin2, as a downstream target of the canonical Wnt pathway, marks tympanic border cells. We took advantage of the Cre-Lox recombination system to temporally label Axin2-expressing tympanic border cells in neonatal mice and follow them over the first 2 weeks of postnatal development.  Our data demonstrate that these cells, despite initially lacking epithelial markers, contribute to the sensory epithelium including sensory hair cells.  Using an analogous Axin2-LacZ reporter mouse strain, we isolated tympanic border cells using flow cytometry and found that they were similarly able to acquire epithelial and sensory phenotypes in vitro.  Although their natural ability to become sensory epithelial cells was surprising, stimulating the Wnt signaling pathway increased their ability to proliferate, similarly to observations made on progenitor cells from other organ systems. Interestingly, there is another population of Wnt-responsive cochlear progenitor cells, the recently characterized Lgr5-positive supporting cells, which are distinct from the Axin2-positive tympanic border cells. This study now suggests that the neonatal cochlea and surrounding tissues may provide niches for multiple progenitor cell populations, a model comparable to many developing and self-renewing organs. Unfortunately either the niches or the progenitor cells (or both) are not maintained into adulthood. This begs the questions of how the two progenitor cell populations relate and interact and how stemness is lost in the mature cochlea. For now, hair cell loss remains irreversible, so think twice about sitting in the front row of the next concert you attend because the noise damage you experience will contribute to the decline of your hearing with time.

(5 votes)

Loading...

The Company of Biologists is sponsoring the next Cosy Science Meeting.  “Jerky or Smooth: The Evolution of Cancer!”, a talk by David Pellman, will be held on March 13th at 7pm at The Cittie of Yorke pub, London.

There will be plenty of time for discussion, and nibbles and free drinks will be provided for the audience!

We hope to see you there!

(2 votes)

Loading...

It was a short month, but a momentous one in the life of the Node: Eva, who set up the site and ran it for the last almost three years, has said goodbye and moved on to new challenges. We’ll need your help to keep things going until her replacement arrives, so please keep posting, commenting and reading!

But there’s been plenty of varied content on the Node this month:

Patricia Gongal is also embarking on a new career, and tested out Science Careers’ “my Individual Development Plan” to see if she’d picked the right job!

Images:
Development is looking for the very best images of stem cells. Submit yours now for a chance to be featured on the cover of Development, or on the upcoming stem cell section of the journal’s website.

This new stem cell competition comes hot on the heels of the most recent round of Woods Hole Embryology Course. This confocal image of an E10.5 day mouse embryo won with over 300 votes.

If you don’t have any images of stem cells for Development’s competition, maybe you have pictures of inanimate objects that look like Xenopus developmental stages. Vicky Hatch set up a Facebook page that features pictures of “Things that look like Xenopus”. They’re everywhere!

Research:
Stephen Frankenberg has been studying early cell lineage specification in the wallaby (a marsupial).

“One of the more interesting findings is that key regulatory factors known from mouse development appear to be uniformly expressed and localised in all cells of the early unilaminar blastocyst, although underlying biases in cell fate could still exist. This raises the possibly that totipotent stem cells could be derived for the first time in any mammal. We plan to explore this and other avenues and hope that our study is just the beginning of a renaissance in marsupial early embryology!”

Jessica Whited works with a completely different animal model. She recently developed a technique for retroviral infection of regenerating axolotl limbs.

“These retroviruses are simply injected into limb tissue, and they can infect any mitotically active cell they encounter. Since the retroviral genomes integrate into host cells, they can be used to permanently express a label such as GFP, which allows for tracking cells during regeneration, opening the door to many future studies.”

Also on the Node:
–Image: Stem cell decisions and the cell cycle
–Breakthrough Prize awards eleven scientists with $3 million each.
–Summary of tweets from the Science Online conference
–Mouse Molecular Genetics conference announcement

(1 votes)

Loading...

Here are the highlights from the current issue of Development:

Cofilin and Vangl2 kick start planar cell polarity

The planar cell polarity (PCP) pathway orients cells within the plane of an epithelium during development. Experiments in Drosophila indicate that the core PCP proteins move to the apical cell membrane during the initiation of PCP and implicate the actin-severing protein cofilin in PCP initiation. Now, on p. 1262, Kathyrn Anderson and colleagues report that cofilin 1 (Cfl1) and the core PCP protein Vangl2 cooperate to control PCP initiation in the mouse embryo. The researchers analyse two aspects of PCP – convergent extension of the axial midline and posterior positioning of nodal cilia. Both these aspects of PCP are nearly normal in Cfl1 and Vangl2 single mutants, they report, but midline extension fails completely and nodal cilia do not polarise in Vangl2 Cfl1 double mutants because PCP protein complexes fail to move to the apical cell membrane. These and other results suggest that remodelling of the actin cytoskeleton is required to traffic vesicles containing PCP proteins to the apical membrane during PCP initiation.

Chromatin remodelling in vein specification

Arteries and veins are structurally and functionally distinct vessels that circulate blood away from and towards the heart, respectively. Notch signalling determines arterial specification during development whereas the orphan nuclear receptor COUP-TFII (also known as NR2F2) promotes venous specification by inhibiting Notch signalling in a subset of endothelial cells. But what regulates COUP-TFII expression in veins? Courtney Griffin and co-workers now report (p. 1272) that the chromatin remodelling enzyme BRG1 promotes COUP-TFII expression and venous specification during mouse embryogenesis. The researchers show that genetic depletion of Brg1 downregulates COUP-TFII expression and leads to aberrant expression of arterial markers in developing veins. BRG1 promotes the expression of COUP-TFII, they report, by binding to regulatory elements within the COUP-TFII promoter and remodelling the chromatin to increase the promoter’s accessibility to the transcriptional machinery. These data describe for the first time a factor that promotes COUP-TFII expression in developing veins and broaden our understanding of how epigenetic processes influence vascular development.

Airn silencing: self-sufficient but reinforced

Epigenetic processes control the parental-specific (imprinted) expression of a subset of mammalian genes. For example, the paternally expressed imprinted long non-coding (lnc) RNA Airn initiates paternal-specific silencing of Igf2r, a gene that is essential for development. Airn initiation of Igf2r silencing is followed by gain of DNA methylation on the silent Igf2r promoter. Here (p. 1184), Denise Barlow, Florian Pauler and colleagues investigate the control of Igf2r silencing during mouse embryonic stem cell (ESC) differentiation. By turning Airn expression off during ESC differentiation, the researchers show that continuous Airn expression is needed to maintain Igf2r silencing until the paternal Igf2r promoter is methylated. By conditionally turning Airn expression on, they show that Airn can initiate Igf2r silencing throughout ESC differentiation and that silencing is maintained in the absence of DNA methylation. Thus, Airn lncRNA is necessary and sufficient to silence Igf2r throughout ESC development whereas DNA methylation is dispensable for silencing initiation and maintenance but reinforces Igf2r silencing.

T cell to myeloid cell switch

T cells develop from multipotent progenitors in the thymus. Initially, these progenitors can generate myeloid cells, B lymphocytes and T cells but, as differentiation proceeds, they become committed to the T-cell lineage. On p. 1207, Marissa Morales Del Real and Ellen Rothenberg investigate the regulatory network that controls this process. Previous studies have shown that the decision to become a T cell can be opposed by the myeloid cell transcription factor PU.1 but that exposure to Notch signalling determines the developmental outcome of expressing PU.1. The researchers now show that Notch signalling does not inactivate the PU.1 protein but instead re-channels its transcriptional effects to maintain a T-cell transcriptional network. They describe two branches of this network – one that involves basic helix-loop-helix E proteins in a positive-feedback loop with Notch, and one in which PU.1 can inhibit T-cell transcription factor genes such as Gata3 only if Notch signalling is absent. Together, these results provide new insights into the complex architecture of a lymphomyeloid developmental switch.

Hear, hear! Postnatal cochlear cell progenitors

Irreversible damage of cochlear sensory hair cells and nonsensory supporting cells causes permanent hearing loss because the sensory epithelium cannot repair or regenerate itself postnatally. Active Wnt/β-catenin signalling marks many endogenous stem cells and Roel Nusse, Alan Gi-Lun Cheng and colleagues now report (p.1196) that tympanic border cells (TBCs), which lie beneath the sensory epithelium, are Wnt responsive and can act as progenitors for sensory epithelial cells in the postnatal mouse cochlea. The researchers show that transient but robust Wnt signalling and proliferation exists in TBCs during the first 3 postnatal weeks and report that Wnt agonists stimulate the proliferation of TBCs in cochlear explants. Moreover, TBCs that express the Wnt target gene Axin2 can generate new hair cells and supporting cells in vivo and in vitro. The researchers suggest, therefore, that TBCs serve as a reservoir of cells for the intricate organisation of the cochlea during early postnatal development and that quiescent TBCs in the adult cochlea might represent targets for regenerative therapy.

Tumour suppression trafficked by Atg6

Autophagy is a conserved catabolic process that degrades the cell’s own components through the lysosomal machinery in response to cell stress. Atg6/beclin 1 is a core component of the mammalian vacuolar protein sorting 34 (Vps34) complex that is required for autophagy. It is also a tumour suppressor, a function that has been attributed to its role in autophagy. But could the potential function of Atg6/beclin 1 in other vesicle trafficking pathways be involved in tumour development? On p. 1321, Eric Baehrecke and co-workers generate Atg6 mutant Drosophila and show that Atg6 is essential for autophagy, endocytosis and protein secretion. By contrast, the core autophagy gene Atg1 is required for autophagy and protein secretion only. Consistent with the tumour suppressor role of beclin 1, loss of Atg6 causes over-production of blood cells and the formation of melanotic blood cell masses. Together, these results suggest that the involvement of Atg6/beclin 1 in multiple vesicle trafficking pathways underlies its role as a tumour suppressor.

PLUS…

Epigenetic mechanisms in the development and maintenance of dopaminergic neurons

Marten Smidt and colleagues review the epigenetic control of mdDA development, maturation and maintenance. See the Review article on p. 1159

Gibberellin signaling in plants

The plant hormone gibberellin (GA) regulates major aspects of plant growth and development. Jean-Michel Daviere and Patrick Achard review the molecular basis of the GA signaling pathway, from the perception of GA to the regulation of downstream genes. See the Development at a Glance poster article on p. 1147

Auxin 2012: a rich mea ho’oulu

In December 2012, scientists from around the world gathered in Waikoloa, Hawaii for ‘Auxin 2012’. At the meeting, participants discussed the latest advances in auxin biosynthesis, transport and signaling research, in addition to providing context for how these pathways intersect with other aspects of plant physiology and development. See the Meeting Review on p. 1153

(No Ratings Yet)

Loading...

The Wellcome Trust – Medical Research Council Stem Cell Institute provides outstanding scientists with the opportunity and resources to undertake ground-breaking research into the fundamental properties of mammalian stem cells.

Salary: £24,049-£27,047

A new post has become available to perform bioinformatic analysis of high-throughput data generated by the research teams of Professor Austin Smith and Dr. Brian Hendrich. The postholder will work alongside a small team of bioinformaticians dedicated to the application of modern bioinformatics techniques to stem cell research. The post holder will interact with bench scientists in the two groups, the SCI bioinformatics team, and with collaborators at the EBI. The projects aim to understand the molecular controls of potency and lineage commitment of embryonic stem cells.
The vacant post is at Research Assistant level and would be suitable for individuals with either a computational or biological background. Necessary training in specialist computational tools will be provided; the main criterion is an enthusiasm to use bioinformatic approaches to advance stem cell research.

The postholder should be able to work in a UNIX/Linux environment. Proficiency with a scripting language (e.g. Perl/Python) statistical analysis tools (R, Matlab) and genome analysis software (e.g. Galaxy) would be a strong advantage.

To apply, please visit our vacancies webpage:
http://www.stemcells.cam.ac.uk/careers-study/vacancies/

Informal enquiries are also welcome via email: cscrjobs@cscr.cam.ac.uk

For more details on the Smith and Hendrich groups, please see:
http://www.stemcells.cam.ac.uk/researchers/principal-investigators/pressor-austin-smith
http://www.stemcells.cam.ac.uk/researchers/principal-investigators/brian-hendrich

Applications must be submitted by 17:00 on 28th March 2013.

We do not accept applications by post or email except in exceptional circumstances. Please note that you cannot amend your application once you have submitted it, so please ensure that you upload all the correct documents the first time.

Application Forms:
All applications MUST include the following:
• Cover Letter
• CV
• The relevant CHRIS form (Parts 1, 2 and 3)
If you do not wish to submit the Equal Opportunities data, please upload a blank form to the applications site.
Interviews will be held week commencing 22nd April 2013. If you have not been invited for interview by 12th April 2013, you have not been successful on this occasion.
The University values diversity and is committed to equality of opportunity.

(No Ratings Yet)

Loading...

Today was my last day as Community Manager for the Node, so this is goodbye from me!

I’ve had a great time these past three years, setting up the site and learning what’s of interest to the developmental biology community.

My favourite part of the job was meeting people in person at conferences and lab visits. It’s difficult to assess exactly how people view the Node from over here in the Cambridge office. Site statistics only tell you so much. But when, two months after launching the Node, two guys walked up to our booth at the SDB meeting in Albuquerque to photograph each other in front of the Node banner, that meant so much more than some anonymous numbers! (I never did get to see those photos. Any leads welcome!)

The more conferences I went to, the more I ran into people who already knew about the Node. Someone told me they saw a poster in their department. Someone else had heard about it at an SDB regional meeting. I’d never been to that department, or to any regional meeting, so that meant that people were spreading the word! And indeed, when we ran a survey in 2011, and asked people how they found out about the Node, “word of mouth” was the second-most popular answer. That, to me, was definitely the best part of the job. A community website is not something you can just build and wait for people to use. The community itself is more important than the technology, and you’ve all been such a great community!

BSDB meeting 2011

Other personal highlights:
-Speaking of community: the 2011 worm meeting. I’m not a worm researcher by any stretch of the imagination, but they were so welcoming!
–Interviewing Jorge Cham of PhD comics. Twice.
–Going viral on Twitter
-Finding people who moved to careers outside academic research, and writing a piece about it for Development.
-Getting Node fan art! (It’s staying in the office, but I’ve got photos!)

The most challenging thing these past few years has been to get across the nature of the Node: people often expected me to update the Node with news relevant to the community, but that is actually something that you should be doing. The Node is meant as a platform for and by developmental biologists, and I’m not one. I was just here to help you find your way. There are currently over 800 people with active Node accounts, who can at any given time post anything they want to the site, without having to ask anyone for permission. It will be a few months until the next Community Manager starts, so I hope that you’ll keep the site filled with interesting things!

I’ll be following along from a distance. A few projects that I started will go live on the site soon. I’m very excited about the next round of Woods Hole images (which I’ve already seen, and which are amazing!) and I’m also looking forward to seeing the first journal club post go up soon!

Thanks to everyone I worked with these past three years – from editors to society staff and from students to lab heads. You’ve all been amazing, and I can’t wait to see where you’re taking the Node next!

If you’d like to stay in touch, you can find me on LinkedIn and Twitter (where my username, @easternblot, reveals my true nature as a biochemist…). I’m moving on to another job that involves a lot of interaction with researchers, in all life sciences, so I hope to see some of you again!

(10 votes)

Loading...