The Revive Postdoc program offers up to 3 years fellowships to young scientists in stem cell research.

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The 8th European Zebrafish Meeting, 9-13 July, Barcelona welcomes proposals from all areas of zebrafish research for consideration for oral and poster presentation.

This meeting will gather together researchers from all over the world to discuss the recent discoveries in the zebrafish field. All communications will be presented either as oral or poster presentations.

Don´t leave your submission for the last minute. We are pleased to remind you that the deadline for abstract submission is March 24, 2013.

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Here are the highlights from the current issue of Development:

Mammary gland RankL-ed into making milk

Extensive remodelling of the mammary gland during pregnancy generates milk-producing lobuloalveolar structures. During remodelling, multipotent stem cells proliferate and differentiate into lineage-committed progenitor cells, which subsequently differentiate into mature epithelial cell types. It has been proposed that progesterone drives mammary stem cell expansion during pregnancy via paracrine signalling from progesterone receptor-positive sensor cells. On p. 1397, Christopher Ormandy and colleagues investigate how the resulting cells are directed towards the secretory lineage. Progesterone induces the expression of the transcription factor Elf5 in mouse mammary progenitor cells, they report, and Elf5 (which is essential for progenitor cell differentiation) cooperates with progesterone to promote alveolar development. They show that the progesterone receptor and Elf5 are expressed in different cell types, and identify the transcriptional activator RankL as the paracrine mediator of progesterone’s effects on Elf5 expression in progenitor cells and their consequent differentiation. RankL also mediates the progesterone-induced division of mammary stem cells. Together, these findings reveal how steroid hormones drive mammary gland remodelling during pregnancy.

Epidermal stem cell heterogeneity

Stochastic fluctuations in gene expression (transcriptional noise), which drive transitions between states, and complex regulatory networks, which define stable interconvertible ‘attractor’ states, are both thought to be involved in the control of stem cell fate. Because population-based studies lack the resolution to reveal the heterogeneity resulting from different attractor states or to uncover their functional significance, on p. 1433 Fiona Watt and colleagues use single-cell gene expression profiling to investigate heterogeneity among human epidermal stem cells. Markers for these cells include the Notch ligand delta-like 1 (DLL1) and the EGFR antagonist LRIG1, but the expression of these proteins is known to vary between cells. The researchers now show that DLL1 expression discriminates between two populations of undifferentiated basal keratinocytes that differ in adhesion and proliferation, and that have distinct transcriptional profiles. These results indicate that intercellular differences in gene expression among human epidermal stem cells cannot be attributed solely to random stochastic fluctuations and suggest that this heterogeneity affects the interaction of these cells with their environment.

Adipocytes and wound healing

Acute wound healing, which restores the essential barrier function of the skin, requires the coordination of the proliferation and migration of both keratinocytes and fibroblasts for epidermal and dermal repair, respectively. Skin healing is known to involve communication between haematopoietic cells, keratinocytes and fibroblasts, but could it involve other intradermal cell types? Barbara Schmidt and Valerie Horsley (p. 1517) have been investigating the involvement of intradermal adipocytes in skin wound healing in mice. They report that immature adipocytes are activated during the proliferative phase of acute skin wound healing and that mature adipocytes appear in healing wounds concurrently with fibroblasts. Moreover, by studying wound healing in mice with genetic defects in adipogenesis and in mice treated with pharmacological inhibitors of adipogenesis, they provide evidence that suggests that adipocytes are necessary for fibroblast recruitment and for dermal reconstruction. Further experiments are now needed to elucidate how adipocytes mediate fibroblast function during the healing of acute skin wounds and to determine whether they also aid the healing of chronic wounds.

Blood vessels guide heart innervation

Peripheral nerves and blood vessels lie close together and have similar branching patterns in many tissues, which suggests that their development might be coordinated. Previously, Yoh-suke Mukouyama and co-workers reported that signals secreted by sensory nerves determine vascular patterning in the skin. Here (p. 1475), the researchers show that there is an anatomical congruence between sympathetic nerves and coronary veins in the developing mouse heart. In contrast to the situation in skin, this neurovascular association is not important for vascular patterning, but is instead required for the functional sympathetic innervation of the heart. Vascular smooth muscle cells (VSMCs) associate with coronary veins during angiogenic remodelling, they report, and mediate the extension of sympathetic axons within the subepicardium by secreting nerve growth factor (NGF). Subsequently, venous VSMCs downregulate NGF expression and arterial VSMCs begin to secrete NGF, which stimulates the axons to innervate coronary arteries in the myocardium. Thus, sequential expression of NGF in subepicardial venous VSMCs and myocardial arterial VSMCs determines the heart’s stereotypical pattern of sympathetic innervation.

Timely BMP patterns neural tube

In many embryonic tissues, graded signals (morphogens) provide the positional information that governs the pattern of cellular differentiation. It is widely thought that cells interpret morphogen gradients by producing corresponding levels of intracellular signalling activity, which regulate differential gene expression. But could other, distinct, mechanisms be used to interpret some morphogens? On p. 1467, James Briscoe and co-workers investigate the morphogen activity of bone morphogenetic protein (BMP) signalling in the chick dorsal neural tube. BMPs are thought to provide the positional information that specifies the spatial pattern of the dorsal interneurons. In neural tube explants, the researchers report, the duration of exposure to Bmp4 generates distinct levels of intracellular signalling and induces specific dorsal identities. Moreover, they find that a dynamic gradient of BMP activity progressively specifies more dorsal identities in the neural tube in vivo. Given these results, the researchers propose a model for morphogen interpretation in which the temporally dynamic control of signalling is required to specify the spatial pattern of cellular differentiation.

Grandmother, what big teeth you have!

Although many organs renew throughout life, the regenerative capacity of some organs varies between species. For example, reptiles replace their teeth continuously, whereas mammals have only a single round of tooth replacement. The development of new teeth involves dental epithelial cells that are competent for tooth formation. Now, Irma Thesleff and colleagues (p. 1424) identify the transcription factor Sox2 as a marker for these cells. The researchers report that Sox2 is expressed in the dental lamina that gives rise to successional teeth in ferrets and humans, which have a single round of tooth replacement, and in five reptiles with continuous tooth replacement. Sox2 is also expressed in the dental lamina during the serial addition of mammalian molars and, in mice, Sox2⁺ cells in the first molar give rise to the sequentially developing second and third molars. These data suggest that Sox2 function has been conserved during evolution, and identify tooth replacement and the serial addition of primary teeth as variations of the same developmental process.

PLUS…

Crossing paths: cytokinin signalling and crosstalk

Cytokinins are a major class of plant hormones that are involved in various aspects of plant development. Recent studies, reviewed here by Helariutta and colleagues, have shown that cytokinins interact with a number of other plant hormones to regulate plant development.

See the Review article on p. 1373

Conserved non-coding elements and cis regulation: actions speak louder than words

The literature is strewn with examples of conserved non-coding elements being able to drive reporter expression, but the extent to which such sequences are actually used endogenously in vivo has been unclear. Here, Nelson and Wardle outline the various methods used to define cis-regulatory elements driving gene expression, and discuss the complex relationship between sequence conservation and the functional equivalence of such elements during development and across evolution.

See the Review article on p. 1385

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WELCOME to the INFORM PhD Program!

The INFORM program (INformation Flow and ORganization at the Membrane) sets up an interdisciplinary consortium at the site of Scientific Park of Luminy in Marseilles, gathering 12 laboratories in Biology, Mathematics and Physics. The objective is to quantitatively understand the biochemical and mechanical basis of cell signaling at different scales from molecular to cellular and tissue levels. The project will allow scientific progress in understanding the dynamics of signaling focusing on a quantitative description of biological mechanisms.

6 PhD fully funded positions will be available for Fall 2013 (aplication deadline May 10th 2013). This PhD program is highly interdisciplinary and based on collaborative projects between partners of the consortium. We encourage graduate students from different backgrounds to apply, biologists but also engineers, physicists and mathematicians.

More details about INFORM project research /technologies and PhD program application procedures can be found on our Website: labexinform.wordpress.com

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Like most things in life, research requires funding. This becomes increasingly apparent as researchers progress through their career. At some point, everyone has to jump on the funding treadmill.

For many researchers, the first experience of a grant application process may be applying for postgraduate funding for their masters/PhD. While I never pursued this option myself, as a postdoc, I now see it from the other side of the fence. It is a good opportunity for PIs to employ someone for 3-4 years at no cost…..Read More

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Like needles in a haystack, interesting speakers that bring charisma and rock n’ roll to their talks are hard to come by. No matter what the research interests of the audience, these speakers hypnotize the audience with their funny analogies and the confidence in their data. Leaving the audience inspired to run back to the lab, read more papers, carry on into post-docing or become a PI…. Read more at www.postpostdoc.com/becoming-a-confident-scientific-speaker

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After a life in science, some of those years getting paid, some of those years not, I decided to set up a website to help PhDs and PostDocs with decisions on what to do next with short shorties of people that have or are going through similar experiences. I also hope to help share a few tips and advice for life in the lab and how to make your work day a little easier! If you are interested please have a look at my website

www.postpostdoc.com

If you would like to get in touch and write and article for the site I would love to hear from you!

Good luck, Good Science!

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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

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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

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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.

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