The community site for and by
developmental and stem cell biologists

Looking for PhD student to investigate how actin regulates YAP activity in skin regeneration and skin cancer

Posted by , on 15 February 2015

Closing Date: 15 March 2021

 

We are looking for a PhD student with experience in Hippo/YAP cell biology, molecular biology and mouse handling, and a keen interest in dermatology and regeneration. Department of Anatomy, School of Medical Sciences, UNSW, Sydney. For inquiries and/or applications, please contact Dr. Annemiek Beverdam (A.Beverdam@unsw.edu.au).

SoMS UNSW PhD Student February 2015

 

Thumbs up (No Ratings Yet)
Loading...

Categories: Jobs

Navigate the archive

Use our Advanced Search tool to search and filter posts by date, category, tags and authors.

Senior Post-Doctoral Research Associate in Nanoformulation Safety Assessment using Xenopus laevis

Posted by , on 13 February 2015

Closing Date: 15 March 2021

Senior Post-Doctoral Research Associate in Nanoformulation Safety Assessment

(to commence May 4th 2015)

University of East Anglia, Norwich, UK, in collaboration with Procarta Biosystems Ltd, Norwich, UK , Consorzio Interuniversitario Per Lo Sviluppo Dei Sistemi A Grande Interfase (CSGI), Florence, Italy and Nanovector, Turin, Italy, are looking to recruit an experienced researcher. The position will be based at University of East Anglia, for 13 months. The position is funded by the European Union under Framework 7 SP3-PEOPLE program, Support for training and career development of researchers (Marie Curie), “Industry-Academia Partnerships and Pathways” (IAPP), Grant Agreement number 612338, DNA TRAP – Delivery of Nucleic Acid-Based Therapeutics for the Treatment of Antibiotic-Resistant Pathogens.

The recruit should have knowledge and experience of performing safety tests on drugs or nanomaterials using in vitro cell culture models and/or in vivo models such as Xenopus laevis or zebrafish.

The candidate should have a PhD degree in cell biology, molecular biology, nanomedicine or developmental biology or at least 4 years full-time equivalent research experience post-degree. Background in Drug development will be particularly appreciated. Moreover, ability to collaborate in a highly multidisciplinary environment is absolutely required (molecular biologists, chemists, industry and academic partners, materials scientists). The candidate should have excellent interpersonal skills and experience of training or supervising others.

The candidate should not have resided or carried out his/her main activity in the UK for more than 12 months in the 3 years immediately prior to his/her recruitment. Short stays in the UK, such as holidays, are not taken into account. This position offers generous remuneration and includes a monthly mobility allowance, based on the family status of the candidate. Applications are invited from all nationalities, and are not restricted to the European Union countries.

Eligible candidates will be selected based on scientific skill and relevance of their research experience to the project and their ability to meet the criteria regarding mobility and research experience described above. This is an equal opportunity position.

These Marie Skłodowska-Curie Fellowship appointments are offered an annual salary of the Sterling equivalent of €78,624 per annum, plus an additional monthly Mobility Allowance of €1344 for candidates who are married or supporting a dependent child, or €941 without. These amounts are subject to UK employment tax and national insurance, including employer’s national insurance contributions and any other employment costs such as employer pension contributions.

Informal enquiries can be sent to: christopher.j.morris@uea.ac.uk or grant.wheeler@uea.ac.uk

Closing date for applications: 6th March 2015

Proposed interview date: 23rd March 2015

Thumbs up (No Ratings Yet)
Loading...

Categories: Jobs

(Developmental) Biology around the internet- February 2015

Posted by , on 12 February 2015

Here is February’s round-up of some of the interesting content that we spotted around the internet!

 

News & Research:

– A new technique called ‘expansion microscopy‘ makes tissues swell up in order to observe structures at higher resolution.

– Mary Lyon, the mouse geneticist who proposed the theory of X-chromosome inactivation, died last December. Obituaries on her life and research can be read in the Guardian and Nature.

– How English became the only language of science– an interesting historical overview in Aeon.

– A recent blog post argued that papers should be written with more style and beauty. Do you agree?

– Plant developmental biologist Caroline Dean is the winner of the 2015 FEBS | EMBO Women in Science Award

– ‘Fly Room‘ is a feature film on the relationship between one of T H Morgan’s students and his daughter, and provides an interesting insight into the early years of fly genetics. The next screening will be at Janelia Farm!

– An opinion piece in Science compared the maternity/paternity leave support for postdocs in the US and in Europe.

– ‘In the 1970s, radical scientists thought they could change the world’- thought provoking article in Mosaic.

– ‘Not your average technician‘- article on Nature News  on technicians with unusual jobs.

– An interesting article in the Guardian discussed the interplay between science and science fiction.

– Christiane Nüsslein-Volhard, the grande dame of developmental biology– article by the Lindau Nobel Laureate meeting

– The Sanger institute released a new website with a variety of educational resources about the genome.

 

Weird & Wonderful:

– ‘Thank you ants for helping me science‘- a cute project shows that the scientific method can be applied by all age groups!

– This xkcd comic explores the gut (macro) fauna.

– Following the success of the Lego Research Institute set, two more science lego projects you can vote for: HMS Beagle and Scientists in History.

– We spotted this fantastic poster/t-shirt from last year’s SDB meeting:

 

   

 
Beautiful & Interesting images:

– We spotted a couple of science cakes in the last few weeks: this muscle fibers cake and a cell division cake

– Is it snowing where you are? Here are some Nobel Prize snowflakes to cheer up your day!  


Videos worth watching:

– What is Evo-Devo and how did this field come to be?- Arkhat Abzhanov explains in this video!

– Is your PI away all the time? This video shows that you are not alone.

– And the Manchester Fly Facility produced this great educational video on the history and importance of Drosophila in biomedical research.

 

 
 
 

Keep up with this and other content, including all Node posts and deadlines of coming meetings and jobs, by following the Node on Twitter

 
 

Thumbs up (3 votes)
Loading...

Tags:
Categories: News

How to eradicate an organ

Posted by , on 11 February 2015

 Phreatichthys andruzzii, lateral view (left), frontal view (right)

Adaptations of some fish species to their environment can be most peculiar, especially within cave dwelling kinds. The so called troglomorphisms slowly turn these fish into almost grotesque looking creatures with no eyes, lost pigments and no scales on the one hand, but with enhanced alternative sensory systems on the other hand.

Cavefish of different orders have been found in cave systems from Mexico to China, all revealing different degrees of adaptations to their life underground. One astonishing example for extreme troglomorphism is represented by the species Phreatichthys andruzii. These fish have been living for about 2 million years in complete darkness in a place, where one would not expect swimming fish at all: under the Somalian desert. Due to this total isolation from surface streams, adult P. andruzzii exhibit full regression of eyes, scales and pigments (see pictures). Remarkably, and similar to the well studied Mexican cavefish Astyanax mexicanus, eyes start to develop during embryogenesis following the stereotypic patterning of eye field determination and subsequent evagination, forming the optic cups. Despite the effort, apoptosis is initiated in later stages and ultimately leads to the loss of the organ. Both species have clearly been evolving separately from each other in two different continents, but concerning the eye loss, the outcome is very similar.

Thus in order to investigate, whether the development is similar on the molecular level as well, or if there maybe are differences, we started an intensive in situ hybridization (ISH) study of key transcription factors and components of regular vertebrate eye development (based on zebrafish and medaka). In the cavefish Astyanax it has been shown that midline signalling of shh (sonic hedgehog) is expanded in early developmental stages, when the eye field is forming, which leads to dysregulation of subsequent transcription factor expression and guidance. When we analysed the early developmental stages of P. andruzzii, we could not detect any obvious deviation of transcription factor patterning and corresponding eye formation. Moreover, when we looked at later stages, we even detected an establishing ciliary marginal zone (CMZ), the teleost stem cell niche of the eye. This observation is further supported by anti-PCNA immunohistochemistry, revealing active proliferation in the CMZ. Taken together, until the onset of further differentiation, the early patterning and formation of the Phreatichthys eyes proceed as in surface species like D. rerio.

From this stage onwards, normal morphogenesis of the vertebrate eye is accompanied by highly stereotypic differentiation of retinal progenitor cells (RPCs), which results in the characteristic layering of the eye. Retinal ganglion cells (RGCs) are born first, 
followed by horizontal, amacrine and bipolar cells and the late-born rod and cone photoreceptors, as well as non-neuronal Müller glia cells. Since no discrete layering of the cavefish retina has been observed at any time point, we studied this developmental phase by addressing cell type specific transcription factor genes with ISH. Our data revealed that only the first born RGCs are established, but not maintained. Detailed analysis of processes of these neurons also revealed no connection to the optic tectum, rendering them functionless. This disruption of the typical differentiation cascade consequently inhibits generation of further cell types and no layering occurs.

Furthermore, we detected massive apoptotic events spreading over the entire neuroretina from this time point onwards, which might very well be triggered by the dysregulated differentiation, in order to protect the eye against aberrant proliferation. Thus, we speculate that a simple differentiation block building on intrinsic control mechanisms elegantly eliminates the Phreatichthys retina.

In comparison to Astyanax, a different strategy is being followed to eradicate the eye during embryogenesis, which specifically blocks differentiation and layering of the neuroretina. In several Astyanax populations this layering proceeds, but apoptosis eventually intervenes, too. By studying these diverse modes of eye degeneration within cavefish species, light can be shed on the different developmental checkpoints and how they are controlled in normally developing vertebrate eyes.

 

Photographs courtesy of Luca Scapoli.
Stemmer, M., Schuhmacher, L., Foulkes, N., Bertolucci, C., & Wittbrodt, J. (2015). Cavefish eye loss in response to an early block in retinal differentiation progression Development, 142 (4), 743-752 DOI: 10.1242/dev.114629

Thumbs up (7 votes)
Loading...

Tags: ,
Categories: Research

Postdoctoral & Technician Position Investigating the Cell Biology of Neurodegeneration

Posted by , on 10 February 2015

Closing Date: 15 March 2021

cover 3One postdoctoral and one technician positions, both fully funded for 3 years, are available in the laboratory of Dr. Natalia Sanchez-Soriano at the Institute of Translational Medicine, Department of Cellular and Molecular Physiology, University of Liverpool, UK. We are seeking highly motivated, collaborative, interactive but independent candidates to study fundamental microtubule- and transport-related mechanisms underlying the formation and maintenance of axons and synapses, and their links to neurodegeneration. Ideally, applicants should be trained in neuro- and/or cell biology, molecular biology and imaging, and have experience with the model organisms Drosophila. For more information about our group see https://sanchezlab.wordpress.com

The laboratory benefits from a highly interactive scientific environment in the Department of Cellular and Molecular Physiology at the University of Liverpool, and an outstanding neurobiology community in the Northeast of England. In addition, Liverpool offers broad cultural and recreational opportunities. Interested candidates should email Natalia Sanchez-Soriano (Natalia1 [at] liverpool.ac.uk) with a statement of interest together with a CV.

Thumbs up (No Ratings Yet)
Loading...

Tags: , , ,
Categories: Jobs

Woods Hole images 2014 round 3- vote for a Development cover

Posted by , on 10 February 2015

Time for the slightly delayed third round of images from the 2013 Woods Hole embryology course! Below you will find 4 beautiful images from the course. Choose the one you would like to see in the cover of Development by voting on the poll at the end of the post (you can see bigger versions by clicking on the images). The poll is set up to allow only one vote per person, so please stick to this rule to give all the images a fair chance!

Voting will close noon GMT on March the 2nd.

 

 

1. Scanning electron micrograph of a black scale from the butterfly, Papilio blumei. Visible is the elaborately sculptured lattice between the microrib-covered ridges. Acting in concert with melanin inside the scales, these scale cuticle nanostructures are thought to contribute to making these scales exceptionally black by trapping light through internal reflection. Imaged on a Zeiss Supra40VP SEM. Distance between ridges is approximately 2 µm. This image was taken by Lara Linden (Duke University, USA).

 

 

2. Blastoderm stage Drosophila melanogaster embryo. In situ hybridization for the 5’ end of Scr in yellow, Antp in blue (from the P1 promotor, 5’ in the first intron), and a previously uncharacterized lincRNA in pink. Imaged on a Leica SP8 confocal. This image was taken by Wiebke Wessels (James Cook University, Australia).

 

 

3. Living embryo of the little skate (Leucoraja erinacea) sitting atop its yolk at approximately ten weeks of development. Imaged on a Zeiss Discovery.V20. This image was taken by Mary Colasanto (University of Utah, USA) and Emily Mis (Yale University, USA).

 

 

4. Wing of the Blue Mountain Swallowtail (Papilio ulysses). The blue scales seen here contain no blue pigment, rather the physical interaction of light with cuticle-based nanostructures of the scale creates a metallic blue color. Imaged on a Zeiss Discovery.V20 with image planes stacked using Helicon Focus. This image was taken by Emily Mis (Yale University, USA) and Misty Riddle (UC Santa Barbara, USA).


Thumbs up (4 votes)
Loading...

Tags: , , , ,
Categories: Images

In Development this week (Vol. 142, Issue 4)

Posted by , on 10 February 2015

Here are the highlights from the current issue of Development:

 

Pathways to human hypothalamic neurons

FigureThe dysfunction of hypothalamic neurons is implicated in a number of common diseases, including obesity, hypertension, and mood and sleep disorders. To date, studies of human hypothalamic neurons have been limited due to their inaccessibility, but now (on p. 633), Florian Merkle, Kevin Eggan, Alex Schier and colleagues use two complimentary techniques to differentiate human pluripotent stem cells (hPSCs) into an array of neuropeptide-producing hypothalamic neurons. In the first approach, the researchers use a self-patterning strategy to generate hypothalamic progenitors from hPSCs (both embryonic stem cells and induced pluripotent stem cells). The subsequent maturation of these progenitors leads to the generation of neuropeptide-producing neurons that are morphologically similar to their in vivo counterparts. In the second, more readily scalable approach, the researchers direct the differentiation of hPSCs into hypothalamic progenitors by modulating pathways known to play a role in hypothalamic development. These progenitors, they report, can also be matured into neuropeptidergic neurons that adopt the gene expression profiles and morphological properties of their counterparts in the human brain. Finally, the authors demonstrate that in vitro-derived human hypothalamic neurons are able to integrate into the mouse brain and continue to express hypothalamus-specific neuropeptides. The cells generated by these approaches thus offer a promising tool for disease modelling, drug screening and therapeutic cell transplantation.

Plant embryogenesis: the ins and outs of auxin flow

FigureDirectional transport of the plant hormone auxin plays an essential role in plant development. To date, most studies of auxin transport have focussed on the PIN family of auxin efflux transporters but now Jiri Friml and colleagues show that the AUX1 and LIKE-AUX1 (LAX) auxin influx carriers are required during plant embryogenesis (p. 702). The researchers first demonstrate that the pharmacological inhibition of auxin influx in both microspore-derived Brassica napus embryos and Arabidopsis thaliana embryos results in defects in early embryogenesis. They further reveal thatAUX1, LAX1 and LAX2, but not LAX3, are expressed during Arabidopsis embryo development. These differentially expressed influx carriers, they report, are required for correct embryo development; patterning defects and defective cotyledon and root formation are observed inaux1 lax1 lax2 triple mutants. Further genetic interaction studies reveal that aux/lax and pinmutations have additive effects on cotyledon development, suggesting that AUX/LAX carriers act in concert with PIN transporters. Finally, the researchers uncover a positive-feedback loop between MONOPTEROS-dependent auxin signalling and auxin transport, highlighting a role for balanced and regulated auxin influx and efflux during plant development.

Morphogenesis in full force

FigureConvergent extension (CE) is a morphogenetic process that shapes the early vertebrate embryo. During CE, embryonic tissues elongate along one axis while narrowing in the other, but how are the appropriate forces generated and regulated during this event? Here, Lance Davidson and colleagues investigate the mechanical control of CE in Xenopus embryos (p. 692). They develop a new method for measuring tissue-scale force production, which involves embedding embryonic tissues in a gel-based force sensor. Using this approach, they report that force production during CE is regulated by myosin II contractility; reduced elongation rates are seen when tissues are treated with a ROCK inhibitor but, surprisingly, these are only evident when tissues are challenged with the mechanical constraints of the gel. By altering gel composition, the researchers further demonstrate that CE is adaptive and can accommodate to stiffer microenvironments, suggesting that mechanical feedback produces greater stresses to overcome the constraints of the gel. Finally, they report that the notochord does not contribute to force production, whereas the paraxial mesoderm and prospective neural tissues are major contributors to elongation forces. This study thus sheds light on the mechanical control of CE and offers an exciting new tool that can be used to probe force production in developing tissues.

Lending weight to mitochondrial transmission

FigureOver-nutrition and obesity during pregnancy are known to result in lasting developmental and metabolic consequences in offspring. Here, using the Blobby mouse model for obesity, Rebecca Robker and co-workers (p. 681) probe the mechanistic origins of these changes and test if they are reversible. They demonstrate that obese females produce cumulus oocyte complexes that exhibit changes in gene and protein expression associated with ER stress. They further show that oocytes from obese mice contain normal levels of mitochondrial (mt) DNA, but display reduced mitochondrial membrane potential and higher levels of autophagy compared with control oocytes. Following in vitro fertilization, the oocytes from obese mice form blastocysts that contain reduced levels of mtDNA and exhibit reduced developmental potential. When transferred to normal-weight surrogates, these blastocysts give rise to foetuses that are heavier than controls and exhibit reduced mtDNA content in the kidney and liver. Importantly, many of these obesity-dependent changes in oocyte characteristics and developmental potential can be reversed by treatment with ER stress inhibitors. Together, these studies demonstrate that obesity induces mitochondrial dysfunction that is transmitted to offspring, and that these defects can be alleviated by using interventions prior to conception to improve embryo and foetal development.

Vascular patterning goes out on a limb

FigureDuring limb morphogenesis, developing digits are initially interconnected by soft tissue but then become separated as this tissue undergoes programmed cell death (PCD) and regresses. Now, Elazar Zelzer and co-workers demonstrate that vascular patterning in the mouse limb regulates interdigital cell death by a reactive oxygen species (ROS)-dependent mechanism (p. 672). They demonstrate the presence of a complex and high-density capillary network within interdigital regions at the onset of PCD; by contrast, the developing digits are unvascularized. As PCD progresses, they report, the vasculature concomitantly becomes remodelled. They further show that a decrease in interdigital blood vessel numbers, induced by inactivating VEGF in the limb mesenchyme, inhibits PCD. By contrast, hypervascularization following VEGF overexpression in the limb leads to elevated PCD and an expansion of the domain in which PCD occurs. Finally, the researchers demonstrate that interdigital PCD is dependent on oxygen and the production of ROS. Together, these findings highlight a novel function for vascular patterning, and suggest the existence of a mechanism by which vascularization of interdigital regions leads to an increase in tissue oxygenation, which in turn triggers ROS production and PCD.

Activin/Nodal signalling in stem cells

DEV607Activin/Nodal growth factors control a broad range of biological processes, including early cell fate decisions, organogenesis and adult tissue homeostasis. Here, Siim Pauklin and Ludovic Vallier provide an overview of the mechanisms by which the Activin/Nodal signalling pathway governs stem cell function in these different stages of development. See the Review on p. 607

 

The melanocyte lineage in development and disease

DEV620Melanocytes have an apparently simple aetiology, differentiating from the neural crest and migrating through the developing embryo to specific locations within the skin and hair follicles, and to other sites in the body. Here, using a cross-species approach, Richard Mort, Ian Jackson and Elizabeth Patton discuss melanocyte development and differentiation, melanocyte stem cells, and the role of the melanocyte lineage in diseases such as melanoma.See the Review on p. 620

Thumbs up (No Ratings Yet)
Loading...

Categories: Research

Friday Harbor Comparative Embryology Course – Applications open until Feb. 26

Posted by , on 10 February 2015

 

Friday Harbor LabsTaking the Comparative Invertebrate Embryology course at the Friday Harbor Labs was one of the pivotal experiences of my graduate life, and it was possibly the most valuable, and enjoyable, course I’ve ever taken. I was a student in the course several years ago, when it was taught by two great scientists, Dr. Charles Lambert and Dr. Mark Martindale (it is taught by different instructors every year). I loved seeing the amazing diversity of marine invertebrate embryos and larvae, and watching their development in real time, after collecting the animals from their natural habitats. One of the things I especially appreciated about the course is that it gave me an opportunity to watch and observe organisms closely, on their own terms, rather than immediately trying to convert them into data points to answer a specific question. This let me see aspects of the embryos and larvae that I would not have noticed otherwise.

 

The Friday Harbor embryology course transformed my research path. At the time I took it, I was a graduate student working on biomechanics and pattern formation in invertebrate colonies, and was more interested in physiology and marine biology than development. I took the course because I felt a need to get a complete picture of invertebrate biology, and it sounded like fun (it was). I loved the complexity of the larvae, with their muscles, ciliated bands, guts, skeletons, and behavior; but as I watched the embryos transform themselves from egg, to blastula, to gastrula, and beyond, I learned to love them for their own sake. At the same time I gained a feel for their variety and for their natural environments.

Pleurobrachia embryoSo, after finishing my Ph.D., I switched from working on adult animals to working on embryos, focusing on the biomechanics of gastrulation in frogs (with Dr. Lance Davidson), and then struck out on my own to study echinoderm blastula formation. The memory of my experiences at Friday Harbor has continued to shape my research, making me think hard about the kinds of variation organisms have to tolerate in nature, variation due to things like salinity, temperature, and maternal condition. And it made me keenly aware of the diversity of developmental processes within and among animal phyla. This gave me a broad perspective on the mechanics of morphogenesis, and how it relates to development-environment interactions and developmental evolution.

 

Hermissenda with eggsMy personal experience in the course led me to my own peculiar niche in developmental biomechanics, but other former students have gone on to study cell and molecular biology, evo-devo, larval ecology, and many other fields. One of the great things about the Friday Harbor course is that it bridges cell and molecular perspectives with ecological and evolutionary perspectives to provide an integrated view of animal development. So the course is very useful for both biologists who wish to understand diversity in developmental modes for ecological or evolutionary studies, and cell and developmental biologists who wish to broaden their knowledge of embryos beyond the standard model systems. The focus is on watching and observing living embryos and larvae from as many different kinds of marine animals as one can get one’s hands on (typically a few species from each of over a dozen phyla).

I loved being a student so much that I jumped at the chance to co-teach the course this summer with Dr. Yale Passamaneck, an excellent evolutionary developmental biologist who has worked with several invertebrate phyla.

Applications are still open, and we have a few spots left that we hope to fill. Applications are needed before February 26th. Financial aid may be available.

If you are interested in the course, please see the course description at: http://depts.washington.edu/fhl/studentSummer2015.html#SumA-4

The course runs from June 15 – July 17, 2015 (5 weeks).

 

Thumbs up (3 votes)
Loading...

Tags: , , ,
Categories: Events

Specifying stem cells, specifically

Posted by , on 5 February 2015

Bone marrow transplants save lives. It’s as simple as that.

The reason bone marrow transplants are so effective is because this squishy tissue is home to haematopoietic stem cells (HSCs), which spend their lives happily producing every single blood cell that will ever circulate around your body.

As a result, if anything goes wrong with your own blood, it is possible to remove your bone marrow (which, for whatever reason, is producing sub-optimal cells) and replace it with somebody else’s which is doing the job just fine.

But it isn’t always quite that straightforward. Finding immunologically compatible tissue isn’t trivial, and there are always more patients needing transplants than there are donors on the list. Also, even if you do manage to find a compatible donor, sometimes their bone marrow just doesn’t contain enough stem cells to be effective.

So, an alternative way of replacing the haematopoietic stem cells in patients with blood disorders is required, and has been the target of many research teams around the globe for years. The golden goal is to be able to generate haematopoietic stem cells in the lab that are genetically matched to the patient, and recent advances in generating induced pluripotent stem cells (iPSCs) from human cells has brought this prospect tantalizingly close – but to date, nobody has managed to successfully generate patient-specific HSCs in the lab.

One major stumbling block in achieving this goal has been a fundamental lack of understanding of how, when and where HSCs actually originate in the first place; how can we possibly attempt to mimic this process in the lab if we don’t know how it works in in a living, breathing organism?

This is exactly the question that scientists in Roger Patient’s lab at the WIMM in Oxford have been asking, and have published their latest findings in Nature Communications.

It is known that during embryonic development of all examined vertebrates, haematopoietic stem cells originate from a layer of arterial cells on the ventral side of the dorsal aorta, known as the haemogenic endothelium [1]. This process is believed to be extremely transient, and is regulated by a complex array of inputs from a variety of signaling pathways, including Wnt16 [2], VegfA [3] and Bmp4 [4].

Role of FGF signalling in the formation of HSCs. Pouget et al, Nature Comms (2014)

Recent research has shown that runx1, a key gene required for emergence of HSCs across many vertebrate species, is directly activated by the Bmp4 signalling pathway in vitro [5], and it is also known that just before definitive (or adult) haematopoiesis is activated in developing embryos, the aortic region switches from a BMP repressive to active environment [4]. However, the mechanism underlying this switch has remained elusive – until now.

Through a series of careful experiments in zebrafish, scientists in the Patient lab have found that the FGF signaling pathway is a negative regulator of HSC emergence via its control of bmp4 activity in the aortic floor, and therefore could be component of the mechanism underlying the switch from a BMP repressive to active environment that is required for HSC emergence.

Not only do these findings add a crucial piece to the puzzle in understanding how HSCs develop in vivo, but could also help to develop more efficient strategies to generate patient-specific haematopoietic stem cells in the lab.

 

The original research article was published in Nature Communications in November 2014: FGF signaling restricts haematopoietic stem cell specification via modulation of the BMP pathway

This post was written by Bryony Graham (@bryony_g) and was originally published on the WIMM blog.

 

1. Swiers, G., Rode, C., Azzoni, E., & de Bruijn, M. (2013). A short history of hemogenic endothelium Blood Cells, Molecules, and Diseases, 51 (4), 206-212 DOI: 10.1016/j.bcmd.2013.09.005

2. Clements, W., Kim, A., Ong, K., Moore, J., Lawson, N., & Traver, D. (2011). A somitic Wnt16/Notch pathway specifies haematopoietic stem cells Nature, 474 (7350), 220-224 DOI: 10.1038/nature10107

3. Leung A, Ciau-Uitz A, Pinheiro P, Monteiro R, Zuo J, Vyas P, Patient R, & Porcher C (2013). Uncoupling VEGFA functions in arteriogenesis and hematopoietic stem cell specification. Developmental cell, 24 (2), 144-58 PMID: 23318133

4. Wilkinson, R., Pouget, C., Gering, M., Russell, A., Davies, S., Kimelman, D., & Patient, R. (2009). Hedgehog and Bmp Polarize Hematopoietic Stem Cell Emergence in the Zebrafish Dorsal Aorta Developmental Cell, 16 (6), 909-916 DOI: 10.1016/j.devcel.2009.04.014

5. Pimanda, J., Donaldson, I., de Bruijn, M., Kinston, S., Knezevic, K., Huckle, L., Piltz, S., Landry, J., Green, A., Tannahill, D., & Göttgens, B. (2007). The SCL transcriptional network and BMP signaling pathway interact to regulate RUNX1 activity Proceedings of the National Academy of Sciences, 104 (3), 840-845 DOI: 10.1073/pnas.0607196104

Thumbs up (1 votes)
Loading...

Tags: , , , , , ,
Categories: Research

BSDB Conference Grant application deadline extended!

Posted by , on 4 February 2015

Conference Grant applications of BSDB members for the BSDB/BSCB Spring meeting can be submitted until Sunday the 8th of February. Please, note that you will require an abstract and support statement as is explained here.

Thumbs up (No Ratings Yet)
Loading...

Tags: ,
Categories: Events, News, Societies