A few months ago, we published an interview with Stephen Fleenor, who won the poster award at the BSDB meeting. He won attendance to the SDB meeting in Montreal, where he passed on the baton and interviewed the winner of the SDB poster prize, John Young:

Stephen Fleenor: In which lab do you work?

John Young: I work in Richard Harland’s lab, at UC Berkeley.

SF: How long have you been there?

JY: I’ve been in his lab for four years, but I’ve been a student for five, because we do rotations the first year.

SF: I see. Well, congratulations on winning the poster prize. What was the crux of the poster?

JY: I’m interested in morphogens. I took a class from Mike Levine when I was a first-year student, and I was totally taken by the dorsal gradient and eve stripe enhancers, and I wanted to do something similar in vertebrates. So I chose to look at the neural plate. The neural plate is first induced to become neural tissue, and then it’s patterned by factors like Wnt, Fgf and retinoic acid. I chose to study Wnt and have been looking at Wnt-responsive genes in neuralized ectoderm. I first looked for direct transcriptional targets of Wnt signalling, and once I found those, I looked for the regulatory regions that mediated Wnt responses in these targets.

SF: And have you found regulatory regions?

JY: Using ChIP-qPCR with beta-catenin I found one regulatory region for one of my candidates that looks really good. Based on that I’m now doing ChIp-Seq with the beta-catenin antibody. I found a lot of direct targets of Wnt signalling, and a number of them showed specific expression in the posterior neural tissue. The two that I followed up with suggest that they modulate AP patterning.

The targets that I followed up after the screen were sall1 and sall4. I chose to work on these two because sall4 is a stem cell factor, and Sall1 has a human mutation associated with it. No one had yet looked at their roles in neural patterning in frogs, though, so I thought they’d be good ones to follow up on.

SF: Sounds like a pretty solid story

JY: It’s coming along!

SF: Have you ever won a poster prize before?

JY: Just at a retreat, and that was second place. This is real!

SF: Was it for the same work?

JY: Yes, it was, but it was a while ago, before things had been fleshed out.

SF: What was the element of your poster that now made it prize-worthy on an international scale?

JY: I think it was that I had knocked down the second Sall gene as well. At first I only had sall1, but now I’m working on both sall1 and 4. And at that time I didn’t have any of the ChIP data either. My project was first to find direct targets, and then I decided to look for the regulatory regions. Finding direct targets was really cool in itself, but it was only half the story.

SF: You’re four years into your PhD research. What are your plans?

JY: I’m going to do a postdoc in Cliff Tabin’s lab. I’m so excited about that, but it’s not until next summer. Now I have a year to finish up this story, and I also need to finish this completely separate project, looking at noggin mutants that I induced in Xenopus tropicalis.

SF: Do you think you’re close to closing the door on the Wnt project?

JY: I think so. I think once we get the beta-catenin ChIP-Seq data back that we can make a nice story out of that. The noggin stuff is not too far off either, so I can get it done in a year.

SF: Are you going to go to the BSDB meeting in Warwick?

JY: Absolutely! I’ve only been to Europe twice – once when I was 15, and in Oslo a number of years ago. I haven’t been to Europe much at all, so I’m looking forward to this opportunity.

At the BSDB meeting in 2013, John will, in turn, interview the winner of the BSDB poster prize.

I’ve just returned from this year’s Santa Cruz Developmental Biology meeting. Some of you may have seen the tweets I was sending out from there (see Storify for the collected set), but a combination of limited ability to multitask and limited laptop battery life meant I didn’t cover all the talks. So to add to what I missed, and for those who prefer more than 140 characters of coverage, here’s a summary of some of the highlights.

SCDB is a bi-annual broad developmental biology meeting, held at the beautiful wooded campus of UC Santa Cruz. With only around 180 participants, it’s a fairly small and very friendly event, with plenty of opportunity for informal discussions. This year, it was organised by Bob Goldstein, Amander Clark and John Tamkun, and topics discussed at the meeting ranged from the evolution of segmentation in arthropods (Mike Akam, University of Cambridge) to ligand/receptor interactions in axon guidance (Elke Stein, Yale University), with pretty much every model organism, tissue and process in between.

Despite covering the whole breadth of the field, there were some definite themes running through the meeting – aside those defined by the program. Multiple talks dealt with the germline: how you make it, put it in the right place and maintain it. Both Diana Laird (UCSF) and Jeremy Nance (NYU Skirball Institute) focussed on the earliest stages of gonad formation in the mouse and the worm respectively. Diana’s work looks at the interactions between migrating primordial germ cells and the various niches they encounter during migration through the embryo, while Jeremy presented data on the mechanisms by which C. elegans germ cells are internalised during gastrulation. Moving to later stages of the nematode, Jane Hubbard (NYU Skirball) demonstrated that nutrient status is a key determinant in regulating germ cell proliferation. The importance of environmental signals was echoed by Timothy Kelliher (Walbot lab, Stanford), who showed that hypoxia triggers germ cell formation in maize (where there is no pre-defined germline as in animals). Perhaps most spectacularly, Bruce Draper (UC Davis) presented his latest work on how mature germ cells influence sex determination in zebrafish: look out for his upcoming paper on sex-changing fish!

As is becoming standard in developmental biology meetings these days, talks were filled with beautiful movies of everything from early stage Drosophila embryos (Dan Kiehart, Duke University and Jen Zallen, Sloan Kettering) to regenerating axolotl (Saori Haigo, Center for Regenerative Therapies Dresden and UCSF) and mouse neural tube closure (Lee Niswander, University of Colorado Denver). But all were (or at least claimed to be!) put in the shade by Eric Betzig’s keynote lecture on super-resolution in vivo imaging: for unprecedented intracellular resolution in developing tissues, the future apparently lies with the Bessel beam.

In a third recurring theme, several speakers discussed the regulation of cell division and its impact on cell fate. Asako Sugimoto (Tohoku University) showed beautiful work on spindle assembly in C. elegans, directly comparing oocyte meiotic division, where the spindle is small and acentrosomic, with the following first zygotic mitosis, in which both centrosomes and chromatin direct microtubule assembly and spindle formation. Laurie Smith (UCSD) uses stomatal development in maize as a model to study asymmetric division, and shared her latest insights into the pathways regulating this process in plants. Finally, Roel Nusse (Stanford University) presented a tour-de-force study on the regulation of embryonic stem cell division by Wnt signalling – another paper to keep an eye out for in the future.

Away from the lecture theatre, the poster sessions were very lively and interactive – congratulations to poster prize winners Shawn Chavez (human blastocyst development), Harshani Peiris (planarian stem cells) and Jacqueline Tabler (ciliopathy models in mouse), although I’m sure there could have been many more winners among the great posters I saw. The Friday evening wine tasting and social session was also enlivened by the surprise entertainment: I’m not sure how many companies get called up and asked if they would sponsor a Mariachi band, but Nikon stepped up to the plate and delivered.

All of this means that the next set of organisers for this meeting – Jeremy Nance, Diana Laird and Amy Ralston – have a lot to live up to: not just in topping the Mexican minstrels, but mainly in putting together a fantastic and diverse set of speakers and fostering a welcoming and collaborative atmosphere. Look out for SCDB2014: I’m sure it’ll be a good’un!

Decisions, decisions.  Stem cells face the task to self-renew or differentiate, a decision made out of the combination and coordination of numerous regulators.  With the activation or suppression of transcriptional activators and the activation or suppression of repressors, it’s easy to see how understanding this process is anything BUT easy.  Today’s images are from a Development paper that describes the importance REST in neural stem/progenitor self-renewal and differentiation.

Neural development begins with neural stem cells and progenitor cells, and follows a specific time-line of differentiation involving neurons and glial cells.  The orderly progression through cell fates requires a complex network of regulators, but the specifics are unclear.  A recent paper in Development describes the importance of REST, a transcriptional repressor of neuronal genes, in the development of the nervous system.  REST, along with its co-repressor CoREST, suppresses neural fates in cells outside of the nervous system.  In this paper, Covey and colleagues found that REST maintains neural stem/progenitor (NS/P) cell self-renewal, and limits maturation into neural and glial cell fates.  In addition, a high level of REST in embryonic stem (ES) cells is important in suppressing transcription of neuronal genes, but is not required for ES pluripotency.  NS/P cells lacking REST have reduced self-renewal capacity and precocious neuronal differentiation.  As seen in the images above, REST heterozygote (middle) and homozygote knockout (right) ES cell-derived neurospheres have increased numbers of neurons (red, TUJ1) compared with control neurospheres (left).  REST null neurospheres also produced fewer astrocytes (green, GFAP).

For a more general description of this image, see my imaging blog within EuroStemCell, the European stem cell portal.

Covey MV, Streb JW, Spektor R, & Ballas N (2012). REST regulates the pool size of the different neural lineages by restricting the generation of neurons and oligodendrocytes from neural stem/progenitor cells. Development (Cambridge, England), 139 (16), 2878-90 PMID: 22791895

48 anatomical structures of the presented mouse embryo atlas are shown in 3D.

Here is the backdrop for our recent paper in Development, “A novel 3D mouse embryo atlas based on micro-CT”.   With the human genome project complete, the sequence and the location of each gene in the genome is understood.  However, the understanding of gene function and the corresponding expressed phenotype for all the genes in the human genome is still in its infancy.  Most of the research aimed to tackle this question will be carried out in the mouse due to the 99% genetic homology between mice and humans and the available techniques to manipulate mice genetically.  Over the last decade, the efforts of a world wide consortium, the International Knockout Mouse Consortium (IKMC, www.knockoutmouse.org), has embarked on a mission to knock out each of the ~23,000 genes in the mouse genome, one at a time, and generate the resultant mice.  With this effort now close to completion another world-wide effort, the International Mouse Phenotyping Consortium (IMPC, www.mousephenotype.org), has been established and the plan on how to phenotype the resultant mice from the IKMC project is being formulated.  What is well understood is that ~30% of the gene knockout mice strains will be embryonic lethal, further accentuating the need for an assay to phenotype mouse embryos throughout development.

If you have two groups of mouse embryos, one wild-type and one mutant, with a single gene knockout, how do you find out what’s different about them?  How do you get clues to the function of the knocked out gene and its role in mouse embryo development?  The most intuitive answer would be to look at the two groups of mouse embryos with a microscope and see if you can find any gross differences in morphology in the mutant group.  You could hypothesize that the organ or structure that shows an aberration in comparison with the wild-type group is an area where that particular gene function is important and carry on with more focused phenotyping assays from there.

This is the exact premise of our recent paper in Development.   Our aim was to eliminate the human bias and time needed to parse through thousands of high-resolution images by developing automated computer methods that could export volume measures of each of the major organ structures within the mature mouse embryo.   We used advanced high-resolution 3D imaging called Micro-CT to image 35 E15.5 C57/Bl6 mouse embryos and developed sophisticated computer software to automatically calculate the mean volumes and standard deviation of 48 structures inside the mouse embryo.  To achieve this, each of the 48 structures within a representative average image of all 35 mouse embryo images were manually painted by one individual, totalling ~400 hours of work.  Through this we acquired baseline volumetric measurements of wild-type mice to determine how tight the variation is among controls.  The resulting labeled data set (the above figure) exists as an E15.5 mouse embryo atlas for which all future mutant strains can be compared with and automatic volume measurements can be executed.  The results presented in this paper, in our opinion, is an important step in demonstrating the feasibility of using 3D imaging as a primary screen in the IMPC pipeline and provides a robust tool that can handle and analyze the large volume of images that will be acquired.

Wong MD, Dorr AE, Walls JR, Lerch JP, & Henkelman RM (2012). A novel 3D mouse embryo atlas based on micro-CT. Development (Cambridge, England), 139 (17), 3248-56 PMID: 22872090

I just came across a press release that looked like it might be interesting to some of you: 1DegreeBio has launched a Stem Cell Portal on its site, that allows you to easily find user reviews and protocols for antibodies used in stem cell research.

1DegreeBio is a relatively new company and the database of reviews is still incomplete, but they do have long lists of antibodies for various targets, and an easy interface for search queries. For example, of the more than two hundred listed antibodies against POU5F1, only two have currently been reviewed by users, and another three were linked to relevant publications.

The search screen

The resource is free to use, though, and if you submit your own reviews of the antibodies you use, you can earn points that you can then spend in their shop, on Amazon gift cards or geeky toys, or donate to charity.

As the number of reviews on the site grow, you’ll be able to make more accurate assessments on the functionality of various antibodies. It seems especially useful for antibodies from certain companies that don’t do any quality testing themselves, but that are sometimes unavoidable when no other supplier sells the antibody you need. I do wonder how 1DegreeBio will be able to ensure that all reviews are done by actual independent researchers, and not left by employees of the companies selling the products, but that is something that might also be less of an issue as the number of reviews grows.

If any of you are using the 1DegreeBio site and their stem cell portal, feel free to leave a comment about your experience. I didn’t sign up myself, because I’m no longer using antibodies, but I’ve gone through many, many vials during my PhD, and have emailed several companies to check species specificity (“Does your human antibody also work with mice?”). If this kind of “Yelp for antibodies” had existed back then I’m sure I would have left many reviews about extreme variation in batch strength, unidentified cross-reactivity, and the few unexpectedly perfect antibodies that saved my thesis.

POSTDOCTORAL  POSITIONS  in  Cell  and  Developmental  Biology  is available to study the cellular and molecular mechanisms controlling the development of the lymphatic vasculature using available mouse models  and  its  functional  roles  in  health  and  disease.  Highly motivated individuals who recently obtained a PhD. or MD degree and  have  a  strong  background  in  molecular  and  developmental biology are encouraged to apply. Interested individuals should send their curriculum vitae, a brief description of their research interests, and the names of three references to:

Guillermo Oliver, Ph.D (guillermo.oliver@stjude.org) Member

Department of Genetics

St. Jude Children’s Research Hospital

332 N. Lauderdale

Memphis, TN 38105

USA

www.stjude.org/departments/oliver.htm

Here are the highlights from the current issue of Development:

eIF4E-3 puts a cap on spermatogenesis

Gene expression is translationally regulated during many developmental processes. Translation is mainly controlled at the initiation step, which involves recognition of the mRNA 5′ cap structure by the eukaryotic initiation factor 4E (eIF4E). Eukaryotic genomes often encode several eIF4E paralogues but their biological relevance is largely unknown. Here (p. 3211), Paul Lasko and co-workers report that Drosophila eIF4E-3, one of eight fly eIF4E cognates, is essential for spermatogenesis. The researchers show that eIF4E-3 is a testis-specific protein and that male flies lacking eIF4E-3 are sterile. eIF4E-3 is required for meiotic chromosome segregation and cytokinesis, they report, and for nuclear shaping and sperm individualisation. The researchers also show that eIF4E-3 physically interacts with other components of the cap-binding complex. Furthermore, many proteins are expressed at different levels in wild-type and eIF4E-3 mutant testes, suggesting that eIF4E-3 has widespread effects on translation. These results add to the evidence that alternative forms of eIF4E add complexity to the control of gene expression during eukaryotic development.

SnoN regulates mammary alveologenesis and lactation

Mammary epithelial cells undergo structural and functional differentiation at late pregnancy and parturition to initiate milk secretion. TGF-β and prolactin signalling act antagonistically to regulate this process but what coordinates these pathways? On p. 3147, Kunxin Luo and colleagues report that SnoN, a member of the Ski family of pro-oncogenic and anti-oncogenic proteins, regulates both TGF-β and prolactin signalling to control alveologenesis and lactation in mice. The researchers show that the expression of SnoN, a negative regulator of TGF-β signalling, is induced at late pregnancy through the coordinated actions of TGF-β and prolactin. Heightened SnoN expression, they report, represses TGF-β signalling, which relieves TGF-β inhibition of the prolactin pathway. SnoN also directly promotes prolactin signalling by stabilising Stat5, a mediator of prolactin signalling. Consistent with these results, alveologenesis and lactogenesis are severely disrupted in SnoN^–/– mice and mammary epithelial cells from these mice fail to undergo proper morphogenesis in vitro unless rescued by active Stat5 expression. Together, these results identify a new role for SnoN in the regulation of lactation.

Co-operative neuronal migration

During the development of the central nervous system, neurons and/or neuronal precursors travel along diverse routes from the ventricular zones of the developing brain and integrate into specific brain circuits. Neuronal migration has been extensively studied in the forebrain but little is known about this key developmental event in the embryonic midbrain (mesencephalon). On p. 3136, Kwang-Soo Kim, Anju Vasudevan and co-workers remedy this situation by studying the migration of dopaminergic (DA) and GABAergic (GABA) neurons in the mouse mesencephalon. They show that DA and GABA neurons follow similar paths to the ventral mesencephalon (VM) in a temporally sequential manner. Interestingly, they report that in Pitx3-deficient (aphakia) mice, which have a defective DA neuron architecture, DA neuron migration is abnormal, stalled DA progenitors fail to reach the VM and GABA neurons also fail to migrate to the VM. These results suggest that pre-existing DA neurons modulate the migration of GABA neurons, thereby providing new insights into neuronal migration and the establishment of brain connectivity during mesencephalon development.

Out on a limb: HoxD chromatin topology

Anterior-posterior patterning of both the primary embryonic axis and the secondary body axis (limbs and digits) in mammals requires regulated Hox expression. Polycomb-mediated changes in chromatin structure control Hox expression during the first patterning event but are they also involved in the second? Here (p. 3157), Robert Hill, Wendy Bickmore and colleagues analyse the chromatin topology of the HoxD gene cluster in immortalised cell lines derived from posterior and anterior regions of distal E10.5 mouse limbs and in dissected E10.5 limb buds. They report that there is a loss of polycomb-catalysed histone methylation and a chromatin decompaction over HoxD in the distal posterior, compared with the anterior, limb. Moreover, the global control region spatially localises with the 5′ HoxD genomic region specifically in the distal posterior limb, a result that is consistent with chromatin looping between this long-range enhancer and its target genes. Thus, the researchers conclude, the development of the mammalian secondary body axis involves anterior-posterior differences in chromatin compaction and looping.

Developmental roles for ribosomal biogenesis genes

Mutations in the human Shwachman-Bodian-Diamond syndrome (SBDS) gene, which functions during maturation of the large 60S ribosomal subunit, cause a disorder characterised by exocrine pancreatic insufficiency, chronic neutropenia and skeletal defects. Steven Leach and colleagues have now refined a zebrafish model of this ‘ribosomopathy’ (see p. 3232). Knockdown of the zebrafish sbds orthologue, they report, fully recapitulates the developmental abnormalities of the human syndrome but, interestingly, unlike in other ribosomopathies, loss of p53 does not rescue these developmental defects. The researchers show that impaired proliferation of pancreatic progenitor cells is the primary defect underlying the pancreatic phenotype and report that loss of sbds results in widespread changes in the expression of genes related to ribosome biogenesis, rRNA processing and translational initiation, including ribosomal protein L3 and pescadillo. Notably, inactivation of either of these genes also impairs expansion of pancreatic progenitor cells in a p53-independent manner. Together, these results suggest new p53-independent developmental roles for ribosomal biogenesis genes.

Mapping the mouse embryo

The sequence and location of every gene in the human genome is now known but our understanding of the relationships between human genotypes and phenotypes is in its infancy. To better understand the role of every gene in the development of an individual, the International Mouse Phenotyping Consortium aims to phenotype targeted gene knockout mice throughout the genome (∼23,000 genes). Because many of these mice will be embryonic lethal, methods for phenotyping mouse embryos are needed. Michael Wong and colleagues are developing such an approach and, on p. 3248, they present a new three-dimensional atlas of the mouse embryo. To produce their atlas, the researchers combined micro-computed tomography images of 35 E15.5 mouse embryos into an average image using automated image registration software, and then manually segmented 48 anatomical structures. This atlas establishes baseline anatomical phenotypic measurements against which mutant mouse phenotypes can be assessed; in the future, a mutant embryo image can be registered to the atlas and its organ volumes calculated automatically.

Plus…

Making waves: the rise and fall and rise of quantitative developmental biology

The tenth annual RIKEN Center for Developmental Biology symposium ‘Quantitative Developmental Biology’ held in March 2012 covered a range of topics. As reviewed by Davidson and Baum, the studies presented at the meeting shared a common theme in which a combination of physical theory, quantitative analysis and experiment was used to understand a specific cellular process in development. See the Meeting Review on p. 3065

A computational image analysis glossary for biologists

Meyerowitz and colleagues present a glossary of image analysis terms to aid biologists and  discuss the importance of robust image analysis in developmental studies.

See the Primer article on p. 3071

Developmental and evolutionary diversity of plant MADS-domain factors: insights from recent studies

Members of the MADS-box transcription factor family play essential roles in almost every developmental process in plants. Kaufmann and colleagues review recent findings on MADS-box gene functions in Arabidopsis and discuss the evolutionary history and functional diversification of this gene family in plants.

See the Review article on p. 3081

With an overwhelming majority, this crisp fly embryo staining won the third round of cover voting, in which readers of the Node chose from images taken in the 2011 Woods Hole Embryology course to select a cover for an upcoming issue of Development.

It shows a ventral view of stage 16 Drosophila melanogaster embryo immunostained for Tropomyosin (green; muscle), Pax 3/7 (blue; segmentally repeated nuclei in CNS and ectoderm), and anti-HRP (red; cell bodies and axons of the nervous system). All nuclei shown in gray (DAPI).

The winning image was captured by Julieta María Acevedo of the Fundacion Instituto Leloir in Argentina, and Lucas Leclere of the Sars International Centre for Marine Molecular Biology in Norway. Congratulations!

The runner-up was an immunostaining of a butterfly wing disk, taken by Alessandro Mongera, Maria Almuedo Castillo, and Jakub Sedzinski. The image of a C. elegans head, taken by Eric Brooks and John Young, got third place, and the final image, of a 3rd instar Drosophila wing disk, was the work of Lynn Kee.

Meanwhile, you’ll see the winner of the previous round on the cover of Development tomorrow, so keep an eye on the journal website.

British researchers working with human embryos for IVF have been wondering about the effects of components of the culture medium they use.

In the UK, culture media used for IVF and fertility research are regulated by the Medicines and Healthcare Regulatory Agency (MHRA) and at European level. Regulation ensures that all researchers and clinicians in the field are using industry standard medium, but manufacturers can change the composition of the media at any time without input from its end users.

When IVF researchers became curious about the role of the various components in the culture medium, and whether the manufacturers could justify changes to the medium, they contacted the HFEA (Human Fertilization & Embryology Authority) – an independent regulatory body in the UK that oversees IVF and related research.

Among many of its other tasks, the HFEA has been trying to make sure that culture medium used for in vitro maturation and preimplantation cultures is safe and optimized for use with human embryos. For example, in 2001, they surveyed IVF clinics about the culture medium they use, mainly to investigate any potential infection risks.

In December 2011, the authority’s Scientific and Clinical Advances Advisory Committee (SCAAC) published a report outlining the current knowledge about the effect of culture media components on embryo viability and development. It’s available on their website.

This most recent report notes that “Although generally considered to be safe based on past and current experience, there are still uncertainties about the long term effects of the culture media used for in vitro fertilisation, and questions remain about the effect of varying components in media. Varying concentrations of components such as growth factors, amino acids, energy substrates, and antibiotics may potentially impact on early embryo development and may have longer term health implications.”

The main conclusion of the report is that, at the moment, the research is inconclusive. They recommend more research into effects of growth medium on early and late development, as well as further investigation into long-term health effects.

The report summarizes some of the studies that have been done to date, which suggest that it’s crucial to keep an eye on what manufacturers add to the media. In one example, an article by Harper et al in Human Reproduction points out that culture medium used in human embryo development was designed based on studies in animal development. It’s not optimized for human development, because for many conditions we simply don’t know what the optimal human condition is. What we do know is that the conditions used in embryo cultures may have long-term effects. They cite a study by Dumoulin and colleagues that showed that different preimplantation media result in differences in birth weight after successful IVF pregnancies. Since birth weight may be associated with disease risk later in life, this research in particular highlights the importance of studying the effect of the various components of culture media.

Studies such as these suggest that any changes in culture media for human embryos need to be assessed very closely. However, the manufacturers of culture media are not obliged to disclose the exact composition of the media they sell. That makes it very difficult to understand the effect of various factors on development.

In an ongoing effort, the HFEA is collecting reports and studies such as these, and is gathering feedback from IVF clinics and researchers. They hope to find out what can be done to ensure that the effects of the culture media used in this field are well-regulated and understood, and plan to communicate their findings to the MHRA.

These studies may take years to complete, especially those assessing long-term effects, but a stronger scientific understanding of the role of in vitro culture medium in human development will eventually translate to a higher success rate and lower risk of IVF procedures.

Harper J, Magli MC, Lundin K, Barratt CL, & Brison D (2012). When and how should new technology be introduced into the IVF laboratory? Human reproduction (Oxford, England), 27 (2), 303-13 PMID: 22166806

Dumoulin JC, Land JA, Van Montfoort AP, Nelissen EC, Coonen E, Derhaag JG, Schreurs IL, Dunselman GA, Kester AD, Geraedts JP, & Evers JL (2010). Effect of in vitro culture of human embryos on birthweight of newborns. Human reproduction (Oxford, England), 25 (3), 605-12 PMID: 20085915

We are seeking to appoint post-doctoral researchers to study microenvironmental regulation of stem cells in mammalian skin.

The aim of our group is to gain a better understanding of the mechanisms underlying the ways in which tissue microenvironments are regionally specialized, and how the specialized microenvironments instruct cellar behaviour and communication, and organ formation. We are particularly interested in the role of the extracellular matrix (ECM) in the formation of the stem cell microenvironment or niche.
http://www.cdb.riken.jp/en/02_research/0202_creative30.html

A recent study by our team has shown that the molecular composition of the basement membrane in mouse hair follicle stem cell niche, the bulge, is highly specialized. One stem cell-derived component, nephronectin, is important for the development and positioning of the bulge-residing arrector pili muscles, which, among other functions, are responsible for goosebumps (Fujiwara et al. 2011. Cell 144, 577-589). This was the first report to show that stem cells regulate the fate and positioning of surrounding niche cells through the specialization of the basement membrane.

To gain further insight into fundamental aspects of the microenvironmental regulation of stem cells, we use mouse skin as a model and seek to better understand 1) the molecular landscape of basement membrane specialization in the stem cell niche, 2) mechanisms by which the basement membrane in the stem cell niche is regionally specialized, and 3) how the specialized basement membrane controls stem cell niche formation, stem cell behaviour and the conversation between stem cells and their neighbouring cells.

Successful candidates will receive an excellent salary commensurate with qualifications and experience. Our Centre, the Center for Developmental Biology (CDB), is a world-leading research institute in the fields of developmental and regenerative biology and has state-of-the-art research facilities. The Centre provides a truly international, collegial, and supportive environment for its nearly thirty laboratories, and the freedom and resources to pursue their research toward deeper understanding of developmental biology. All necessary communications can be conducted in English, and support services are available for non-Japanese-speakers.

Please contact Hironobu Fujiwara, PhD (hironobu.fujiwara@cancer.org.uk) for further information.

To apply, please send 1) a cover letter, 2) a CV with publication list, 3) names and contact details of two referees, 4) a brief summary of research achievements and future research interests (two page maximum) to Hironobu Fujiwara (hironobu.fujiwara@cancer.org.uk) via email. Please send the application as a single PDF file. This call will be closed when the positions are filled.