I am the founder and CEO of DataGiving. I founded DataGiving whilst completing my Ph.D. in Genetics at the University of Cambridge. I have always been passionate about helping people. After completing my Bachelors degree in Psychology, I worked as an Assistant Psychologist at St Marys Hospital in London, helping adults with severe mental health disorders. Since I was a teenager I had aspired to become a Clinical Psychologist, but as much as I admired the great work Psychologists do, I didn’t feel that my desire to reach out and make a positive change would be fully achieved in this role. I returned to academia, as I had long been intrigued to learn more about the biological basis of human behaviour and cognition. I completed a Masters degree in Cognitive Neuroscience, at Imperial College London, which included a laboratory based research project at the Hammersmith Hospital, investigating the genetic basis of Parkinson’s Disease This research sparked my passion for genetics, and specifically the field of Epigenetics. I went on to be awarded an MRC scholarship, to undertake research into the imprinting regulation of Gsα in the laboratory of Dr Gavin Kelsey at The Babraham Institute, Cambridge.

Whilst at Cambridge, I was determined to fully participate in both academic and social life Cambridge University had to offer, and I served on my College graduate committee, was editor for the Graduate Union Bulletin, and was responsible for raising sponsorship for the Cambridge University Entrepreneurs Society (CUE). At Cue, I learnt about what was required to develop successful businesses, and met fellow students interested in entrepreneurship. I also worked for a while for a biotech, identifying collaborative opportunities with research labs around the world.

I have long been an advocate of harnessing creative and innovative technologies, to facilitate change for the common good. After a period of teaching myself basic computer programming, myself and a team of fellow Cambridge graduates won the TedxCam 2010 Open Data Challenge Hackathon, with a web data mashup named Ventropy (www.ventropy.org). Described by the BBC as “jaw-dropping”, Ventropy impactfully communicates the needs of grassroots businesses in mainly developing countries looking to raise funding through the microfinance site Kiva. Ventropy received high-praise from leaders from both the technology/web and charity fields, and is featured in the Kiva app portal. I was invited to speak about the inspiring idea at The Guardian Activate 2010 Summit, Technology, society and the future: Changing the world through the internet.

I went on to be awarded an UnLtd HEFCE Social Entrepreneurship Catalyst Award to develop the idea of Ventropy into a data visualisation app that translates the charitable impact of any amount of money, this can be seen at www.datagiving.com.

I am passionate about inspiring social entrepreneurs, and earlier in the year I was invited to speak to students at Cambridge University interested in ethical careers at the Beyond Profit flagship event, ‘From dream to reality – funding and support for social enterprise’, alongside UnLtd CEO Cliff Prior. I was also invited back to The Guardian Activate Summit in 2011 to take part in a stimulating panel debate discussing the power of data to save the world.

My scientific training has equipped me with an analytical mindset and curiosity that I’m able to apply in wider contexts of innovation. I am still very much passionate about biological science and in encouraging innovation in this field. I recently came runner up in an Open Innovation competition organised by MedImmune and Cambridge University Technology Enterprise Club, and I have since been asked by MedImmune to develop an Open Innovation strategy for MedImmune and the University of Cambridge.

My career to date has taken unexpected and unconventional twists and turns, but I’ve enjoyed every moment. Keeping an open mind and carving out your niche can be hard work, but incredibly rewarding.

(7 votes)

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There’s an interesting interview in Nature News, with Abdelali Haoudi – the vice-president for research of the Qatar foundation. Qatar opened a biomedical research institute a few years ago, and is now looking to expand this with a stem cell institute.

The situation in Qatar is almost opposite of that of many other countries:  they have enough money to set up the institute, but not necessarily enough highly-skilled people to work there. They’ve sent six students abroad to learn about stem cells at top institutes, and expect them to come back to work in Qatar, but will they really all come back, or is this going to be a practical lesson in the risks of “brain drain”?

The interview also addresses the ethical aspects and Islamic views of stem cell research. The foundation organised a conference for Islamic scholars to determine the fatwa (official Islamic rules) concerning human embryonic stem cells, and they came up with a set of well-defined rules: “We can use tissues from embryos for up to 14 days after fertilization. We have to get the consent of the parents. We cannot create embryos specifically for research, and we cannot use the tissues for commercial purposes — only for basic research or to develop new therapies”, explains Haoudi.

Have a look at the entire interview.

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The Embryology course at Woods Hole is still ongoing, and you can read more about what they’ve been up to so far in David Gold’s post.

The images below are the last of last year’s course images that have a chance at appearing on the cover of Development. Which of these images will be next to appear on the cover? Please vote in the poll below the images. (Click any image to see a larger version.) You can vote until July 26, 12:00 (noon) GMT

1. Drosophila larval body wall stained for tropomyosin (red), acetylated tubulin (green) and nuclei (blue, DAPI). This image was taken by Sylvia Bonilla (Purdue University) and Mazdak Lachidan (Samuel Lunenfeld Research Institute, Toronto).

2. Ciona embryo electroporated with Brachyury:RFP transgene. Nomarski image was used to create green overlay. This image was taken by Qinwen Liu (University of Maryland, College Park) and Xinwei Cao (St. Jude’s Children’s Research Hospital).

3. Mouse embryo. Wnt1/Cre-YFP transgene (yellow), 2H3 antibody (red), and DAPI (blue). This image was taken by Elsa Denker (Sars International Centre for Marine Molecular Biology, Bergen).

4. Live late stage squid embryo. This image was taken by Amber O’Connor (University of Alabama at Birmingham).

(3 votes)

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Twenty-four of us have been working for the past five weeks, studying development in a variety of contexts and organisms at the Marine Biology Laboratory in Woods Hole, Massachusetts.  The area is beautiful, but we don’t have much time to enjoy it.  This is a very intense course, we have lectures from 9am to noon, and then work on experiments often until 1 or 2 in the morning!  Because of this, we have been a little slow getting our blogposts going, but we look forward to sharing our experiences from Woods Hole.

Our course directors, Nipam Patel and Lee Niswander, presented the Embryology course as a chance to work with the latest techniques on model organisms (such as mice, and fruit flies), while providing a broad introduction to the diversity of animal evolution.  The first two weeks of the course exemplified these dual goals, as we studied some of the earliest branching animal lineages, and the two major invertebrate model systems.

At the beginning of the course Nicole King came to teach us how to work with choanoflagellates and sponges, while Uli Technau introduced us to the cnidarians (in particular the sea anemone Nematostella and the hydrozoan Hydractinia). Sponges and cnidarians are morphologically much simpler than most animals, and genetic evidence supports the long-standing hypothesis that they were some of the first groups to diverge from our own lineage.  However, sponges and cnidarians possess many of the genes  “higher” animals have, and they have provided important insight into the ways cells communicate during development.

Choanoflagellates are not actually animals, but DNA evidence suggests that they may be animals’  closest living relatives. Each choanoflagellate is a single cell. It has a long flagellum, which it uses to swim through the water and to trap bacteria (which it eats) in a collar made up of microvilli. The reason that choanoflagellates have received a lot of attention recently is that they don’t always spend life as a single cells.  Sometimes, as a choanoflagellate divides, the individuals stay connected to each other in long chains or rosettes.  Perhaps these organisms can teach us how the first multicellular animals evolved. Below is an image created by classmate Valerie Virta showing single and colonial choanoflagellates, the blue is staining the choanoflagellate bodies (DAPI), the red is microvillar collar (actin) , and the green is the flagellum (tubulin):

A team of scientists, including Joel Rothman, Dave Sherwood, and David Fitch, then came to teach us about the roundworm Caenorhabditis elegans. C. elegans has become a important model for understanding basic development.  Dave Sheerwood, for example, gave a great lecture on how the developing vulva of C. elegans may provide a better model for studying cancer than cultures of human tissues (you can find a podcast about his work here; look for the podcast from 5/10/10).

Finally, we got our hands on the invertebrate workhorse of genetics and developmental biology, the fruit fly Drosophila melanogaster.  It’s exiting to think that Thomas Hunt Morgan, the Nobel Prize winning founder of fruit fly genetics, did much of his research at the same institute we are working at now.  Nipam Patel, Lynn Cooley, Iswar Hariharan, and Matt Ronshaugen showed us a number of techniques for visualizing development, gene expression, and miRNA exoression in D. melanogaster, as well as how those techniques could be modified to look at other arthropods.  Below is a movie taken by David Gold of several Drosophila imaginal disks, stained with eyeless, cubitus interruptus, teashirt, and dapi:

We look forward to updating you with details about the third and fourth weeks soon.  More detailed posts will be available over time from David Gold’s blog at www.BioBlueprints.com.

(7 votes)

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Since its launch in June 2010, the Node has attracted thousands of visitors. Some have visited only once, others return every day. Some have written on the site, others only read. No matter which group you belong to, we now want to hear from YOU how your experience on the Node has been.

We’ve created a short survey, which should take no longer than 8 minutes to complete, to learn more about the Node’s readers, and find out how we can improve the site. The Node was launched in response to feedback from a community survey run by Development, so you can be sure that we take your feedback seriously in considering how to further develop the Node.

To thank you for your time and help, we’re holding a draw for a gift pack containing various items from the Node and Development – but you’ll need to complete the survey to be eligible!

Take the Node survey here.

We will be collecting responses until July 26th.

(1 votes)

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As promised, in this final part of my meeting report on the BSCB-BSDB Spring Conference 2011 I will highlight a couple of talks which came with visual effects – studies involving live imaging. I prefer to watch these movies in seminars rather than downloading them with a paper because getting live explanations can make things clearer and more memorable for me. Drosophila was the main movie star, so this post will cover only fly studies.

Lucy Morris, a postdoc in Allan Spradling‘s lab (Carnegie Institution, Baltimore, USA), managed to develop a culture system that keeps the Drosophila germarium (the anterior tip of the ovariole) alive and developing for 14 hours. She used this to follow ovarian follicle generation in real-time: Every 12 hours, a new follicle is generated from a germline stem cell (GSC), which divides and migrates posteriorly, forming a cyst of 16 germline cells. While doing so, the cyst is wrapped by somatic escort cells, which midway through the germarium are replaced by a monolayer of somatic follicle cells. Escort cells have been proposed to arise from an escort stem cell niche at the anterior tip of the germarium and migrate along with the cyst, undergoing apoptosis after being shed. However, in her movies Lucy did not observe high levels of escort cell apoptosis, divisions or net migration! Rather, escort cells stayed still and let germline cysts pass them by using dynamic membrane protrusions to help them along. Lucy also found that escort cells do undergo rare divisions, but do so only to maintain a constant ratio of germ cells to escort cells.

After shedding the escort cells, the cyst is coated by a monolayer of follicle cells, which continue to encase the egg chamber until the egg is formed. This follicular epithelium carries integrins on its basal surface, which connect to the cytoskeleton and thereby mediate follicle cell migration over the extracellular matrix. Nick Brown (Gurdon Institute, Cambridge, UK) and his group imaged the movement and morphology of wild-type and mutant follicle cells to gain insight into the functions of specific integrin-associated proteins during this process. They identified a complex of proteins downstream of integrins that regulates actin stress fibres during a specific time point in development, leading to a sudden switch in the distribution of dynamic actin protrusions and a subsequent stop in migration – an observation that would have been impossible to make using fixed specimens only.

Arno Müller‘s (University of Dundee, UK) lab is interested in the mechanism of mesoderm layer formation and he presented movies in which they monitored the dynamic changes in morphology that the cells undergo during these tissue rearrangements. They found that the mesoderm cells change their migrational behaviour and morphologies during the process, with the consecutive phases having different requirements for the two FGF ligands, Pyramus and Thisbe.

Finally, germ-band extension was featured in more movies from the embryo, presented by Bénédicte Sanson (University of Cambridge, UK). During this process, the embryonic trunk elongates in the antero-posterior axis and narrows dorsal-ventrally. Bénédicte’s lab imaged the surface of wild-type and mutant embryos and automatically tracked cell movements and shapes to explain which cell behaviours lead to the net tissue deformation. These movies provided them with the data to conclude that both cell intercalation and cell shape changes contribute to the deformation in the fast phase of germ-band extension, whereas in the subsequent slower phase only cell intercalations are required. Polarised cell intercalation is directed by antero-posterior patterning, an intrinsic “force”. The changes in cell shape however can be explained by the invaginating mesoderm acting as an extrinsic force. Bénédicte therefore proposed that a balance between these two forces is essential for axis extension.

I learned from these and other talks that if you would like to know how cells behave in a tissue you will have to try to image them. Not only does this frequently result in spectacular movies, it also provides a lot of information in a very short time. Of course the imaging protocol first has to be established, a task that admittedly can present a whole PhD or postdoc project on its own – but more often than not, it seems to be worth the effort.

Morris LX, & Spradling AC (2011). Long-term live imaging provides new insight into stem cell regulation and germline-soma coordination in the Drosophila ovary. Development (Cambridge, England), 138 (11), 2207-15 PMID: 21558370

Clark IB, Muha V, Klingseisen A, Leptin M, & Müller HA (2011). Fibroblast growth factor signalling controls successive cell behaviours during mesoderm layer formation in Drosophila. Development (Cambridge, England), 138 (13), 2705-15 PMID: 21613323

Butler LC, Blanchard GB, Kabla AJ, Lawrence NJ, Welchman DP, Mahadevan L, Adams RJ, & Sanson B (2009). Cell shape changes indicate a role for extrinsic tensile forces in Drosophila germ-band extension. Nature cell biology, 11 (7), 859-64 PMID: 19503074

(2 votes)

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Last week I attended the 18th international C. elegans meeting at UCLA, organised by the Genetics Society of America. Having done most of my scientific training with mammalian cell culture, I had never been to an organism-specific meeting – let alone one about worms – and I was curious to find out what it would be like. I also wanted to learn more about the sense of community that exists among worm researchers, and what better way to experience that than by visiting their conference.

After the first day of talks, I had already spotted the community spirit in the presentation acknowledgements. The speaking slots were 12 minutes – 10 minutes to present, 2 for questions. That’s not exactly a lot of time to dwell on thanking everyone at the end, but they all did. In particular, almost everyone thanked the Caenorhabditis Genetics Center (CGC) for strains. However, in one of the opening talks of the meeting, Aric Daul of the CGC showed that people do tend to forgot to credit the centre in their publications. Since publication acknowledgements are a metric to ensure their continued funding, he urged people to not just thank the CGC in their talks, but also in their articles.

But nowhere was the community spirit of the worm people more obvious than in the social events. First of all, there were so many of them. I didn’t even manage to attend them all, but even after skipping two post-poster session socials, I still made it to the barbecue dinner, the Worm Art Show, the Worm Comedy Show, and the closing party. The party was unlike any conference party I had ever been to. Instead of the usual small wooden floor in a brightly lit dining hall, the worm party involved a huge ballroom, disco lights, and a packed dancefloor. Earlier that evening, the Worm Comedy Show, with Morris Maduro and Curtis Loer, had everyone laughing along at “The Lab” (a parody of the comedy “The Office”) and fake advertisements full of geeky humour (“UGG Tryptophane Boots”), and even singing along to “This Worm is My Worm”. The comedy show came just after the announcements of the Worm Art Show awards, but I’ll feature those in a separate post to highlight some of the art work.

There was science, too, of course. I attended most of the developmental biology sessions, but there were often two interesting talks at the same time. Still, thanks to modern technology you don’t have to miss a thing anymore: The meeting organisers encouraged people to use Twitter to share the meeting, and through there I could often see a glimpse of one of the parallel sessions. In fact, thanks to people eagerly tweeting bits of the meeting, I’ve managed to create a collaborative impression of the conference using Storify. See below to see the C. elegans conference through the eyes of Twitter users. (Make sure to click “load more” at the bottom. If nothing shows up below this paragraph, refresh the page. I’m new at using Storify so haven’t figured out if there’s a way to make it smaller on screen.)

(4 votes)

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Exactly one year ago today, we launched the Node. Since then, we’ve accumulated a good number of regular readers, and some enthusiastic contributors. We’ve covered meetings, research, news, images and other topics – all with a focus on developmental biology.

It seems like this past year just flew by. Really, where did the time go?

To make sure we keep better track of time in the remainder of 2011, we’ve created a set of downloadable desktop calendars. For each month from July to December 2011 you will be able to download a calendar with an image that has previously appeared on the Node.

The first desktop calendar, for July, is up now, and features the winning image from the “intersection” contest we had on the Node a few months ago. It shows a co-localization of slow myosin heavy chain (magenta) with Sox6 (in blue) on a gut section of a E17.5 mouse embryo. Image by Stéphane Vincent of the IGBMC.

Click one of the links below to go to a full-size image..

1024×768 | 1280×1024 | 1920×1200

We have three sizes available to accommodate common screen resolutions. Select the correct size above or on the calendar page. The page will be updated at the end of each month with a new image, and all images are chosen from either the intersection image contest or from the images we’ve featured from the Woods Hole Embryology 2010 course.

(9 votes)

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If I shut my eyes, I can still picture  the young boy dressed as a gravedigger. He’s taking centre-stage, flourishing a spade and cheerily telling his audience that if they don’t practise safe sex, they will die of AIDS and boost his business. It’s not the sort of thing you expect from a Sunday school play.

It was February 2002 and I was in Kenya, covering a story for New Scientist magazine about how traditional African theatre could help teach local people about HIV, food hygiene and environmental threats such the pollution of nearby Lake Victoria. The science conveyed in the plays was basic, but it had the power to transform people’s lives.

That reporting assignment, which also took me to Nairobi’s slums and into the African Rift Valley to meet the Maasai people, is probably the most challenging of my career. It taught me how much you can achieve with nothing more than a notebook, pen and a pocket camera. It also sealed my conviction that sharing scientific knowledge is as valuable an enterprise as generating it.

I certainly didn’t start out with the idea of becoming any kind of journalist. The developmental biology bug bit during my undergraduate degree and I decided to pursue a career in research. Funded by a Prize Studentship from the Wellcome Trust,  I joined Helen Skaer’s lab, then at the Department of Human Anatomy in Oxford, in 1995. Under Helen’s excellent tutelage, I started work on finding out how the cells of the Drosophila renal system, the Malpighian tubules, decide their fate.

But while I was happily dissecting embryos, two things changed the course of my career. The first was a science communication course run by the Wellcome Trust for its Prize students. One of the course tutors, Peter Evans, a science radio journalist for BBC Radio 4, encouraged me to try my hand at student radio. Before long, I was a writer and presenter for The Frontier, a science magazine show on Oxygen 107.9FM, the UK’s first student station with a full FM radio licence.

I have no idea how many listeners  The Frontier team had, but producing a live half-hour show every week, whilst also studying for our degrees, was both hugely stressful and immensely fun. It planted the idea that this might be something I could do in future. To test the waters a bit more, I entered a number of science writing competitions, and was a runner up in the Wellcome Trust / New Scientist Essay competition.

This prompted the second career-changing event: as I was writing up my doctoral thesis, I applied for an internship as a subeditor at New Scientist. I succeeded in getting the job and joined the magazine as soon as my lab work was complete.

Working on a magazine was worlds away from counting Malpighian tubule cells, but the experience of working on The Frontier, as well as the writing competitions, did help–both in terms of doing the job and getting it in the first place.

So if I could only give one bit of advice, it would be this: if you want to get into science journalism, just do it. Take every opportunity you can–blogging, writing competitions, student newspapers or radio, writing for trade or academic publications, working as an intern–to flex your writing muscles and build a portfolio of examples to show prospective employers. Plenty of people say they want to be science journalists, but far fewer demonstrate the initiative and nous required to make it happen.

Subeditors are unsung diamond-polishers of the publishing world; their job is to edit prose for clarity, good grammar and style and then write eye-catching headlines. Being a trainee sub taught me a great deal about how to write well and fueled my desire to become a reporter / writer myself. I started writing pieces for the magazine and within a few months, I had wangled a job as a reporter in New Scientist’s news section.

I stayed in News for about 18 months before finding my métier as a feature writer, and eventually I became a features editor. Features are longer articles that give you the time and space to explore ideas in more depth and craft an article into more of a story, both of which appealed to me. In 2005, I left New Scientist to join Nature as a senior reporter and editor, where I focused on developing the biology features in Nature’s news section.

While this was all happening, I had been using my annual leave to train scientists in science communication skills, with my marine biologist husband, Jon Copley. There is an increasing demand for researchers to communicate with the public and to demonstrate the impact of their work. So Jon and I founded a company called SciConnect to offer training courses in these areas to scientists who need them.

By the time I had been at Nature for two years, the demands of SciConnect were growing. What’s more, I found that I was spending most of my time editing rather than writing. Much as a enjoyed working at Nature, I decided to leap into the unknown and become a freelance science journalist and full-time managing director of SciConnect. After I handed in my notice, I lay awake all night, fretting about whether I had just made the worst mistake of my career.

I need not have worried. Running my own company and freelancing as a writer has been terrifying, exhilarating, overwhelming, and empowering, in turn. It demands a whole new skill set and the learning curve has been precipitous. But it has its rewards: SciConnect has now equipped more than 1600 scientists, from PhD students to Profs, with the skills to share their work with the world.

There are days of doubt, of course. Every now and then I fish a sozzled fruit fly out of my Rioja, dry its bright wings and feel a pang of nostalgia for the lab. Or I’ll encounter a snotty academic dinosaur (thankfully a rare species) who thinks that “journalist” means “imbecile” and that leaving the research track somehow equates with failure or “dropping out”.

At times like these I remember the jolly little gravedigger and remind myself that science is not just about making discoveries, but also holding science to account and making sure those discoveries reach beyond the lab.

If anyone is contemplating making the leap into journalism, check out the career information on the Association of British Science Writers’ website.

Alternatively drop me a line via email (info@sciconnect.co.uk), on Twitter (@ClaireAinsworth) or my blog and I’ll do my best to help.

(13 votes)

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Here are the research highlights from the current issue of Development:

How to make stripes: revising the pair-rules

A key step in Drosophila segmentation is the transition from non-periodic to periodic gene expression patterns, a process that is controlled by transcriptional regulation of the pair-rule genes. Primary pair-rule genes generate their striped expression patterns through stripe-specific cis-regulatory elements that are controlled by the preceding maternal and gap gene expression patterns, whereas secondary pair-rule genes establish their stripe patterns in response to positional cues already provided by the primary pair-rule genes. On p. 3067, Ulrike Gaul and colleagues use computational and experimental approaches to systematically reappraise the complex regulatory architecture that underlies pair-rule stripe formation and, based on their analyses, reclassify fushi tarazu and odd skipped as primary rather than secondary pair-rule genes The researchers also present results that point to a much closer integration of maternal/gap-mediated and pair-rule-mediated regulation than previously recognised and provide new insights into the function of stripe-specific cis-regulatory elements. Together, these results deepen our understanding of periodic pattern generation in the Drosophila embryo.

Sprouty limits cerebellar FGF signals

The fibroblast growth factor (FGF) pathway is active in several cell types within the developing cerebellum. During early embryogenesis, FGF signalling helps to establish cerebellar territory but its function during later development is unclear. Now, on p. 2957, M. Albert Basson and colleagues report that the normal development of several cell types in the mouse cerebellum depends on tight regulation of FGF signalling by sprouty genes, which encode feedback antagonists of FGF signalling. Spry1, Spry2 and Spry4 are expressed in the developing cerebellum. The researchers show that simultaneous deletion of multiple sprouty genes results in numerous cerebellar defects, including abnormal folding of cell layers and reduced granule cell proliferation. Reducing the Fgfr1 dosage rescues these abnormalities, confirming that they are due to excess FGF signalling. Moreover, the effects of deregulated signalling on cerebellar morphology depend on the time and cell type in which sprouty genes are deleted. Thus, suggest the researchers, FGF signalling has several distinct functions and must be tightly controlled during cerebellar morphogenesis.

Chemokine evolution and development

During development, families of ligands and receptors control concurrent processes, but how do cells discriminate between closely related signals? To find out, Erez Raz and co-workers have been studying chemokine signalling during primordial germ cell (PGC) migration in zebrafish embryos (see p. 2909). In vertebrates, the chemokine Cxcl12, which binds the Cxcr4 receptor, guides PGC migration. Zebrafish express two Cxcl12 paralogues and two Cxcr4 receptors. The researchers report that, although PGCs can respond to both Cxcl12 ligands, only Cxcl12a, which exhibits a higher affinity than Cxcl12b for one of the receptors (Cxcr4b), guides the cells. Moreover, a single amino acid exchange switches the relative affinity of the Cxcl12 ligands for the duplicated Cxcr4 receptors, allowing each chemokine to elicit a distinct effect. The researchers suggest that the subfunctionalisation of the cxcl12 genes that followed their duplication occurred through alterations in their expression patterns and in the specificity of receptor binding. Subfunctionalisation of this sort, they suggest, could enable chemokines and other receptor-ligand families to control concurrent developmental processes.

Top-Notch trophoblast vascular invasion

During placental formation, trophoblasts invade and remodel uterine vessels in order to re-route maternal blood to the placenta to nourish the developing embryo. This process fails in pre-eclampsia, a serious but common pregnancy complication. Here (see p. 2987), Susan Fisher and colleagues report that Notch signalling plays a key role in trophoblast endovascular invasion. By immunostaining human placental tissue sections, the researchers show that Notch receptors/ligands are modulated in a stepwise manner during trophoblast invasion. Inhibition of Notch signalling reduces invasion of cultured human trophoblasts and expression of the arterial marker EFNB2. Similarly, in mice, conditional deletion of Notch2 reduces arterial invasion, the size of maternal blood canals and placental perfusion, and leads to litter-wide lethality. Finally, in placental tissue sections obtained from women with pre-eclampsia, expression of the Notch ligand JAG1 is absent in perivascular and endovascular trophoblasts. Together, these results indicate that Notch signalling is crucial for trophoblast vascular invasion and that Notch signalling defects are involved in the pathogenesis of pre-eclampsia.

Getting to the heart of epicardial potential

Regenerative medicine could provide treatments for heart disease but a source of cells capable of regenerating cardiac muscle cells remains elusive. One possible source is the epicardium, but lineage-tracing studies have produced conflicting results about the extent to which epicardial cells act as a natural source of cardiac muscle during development. Now, on p. 2895, Kazu Kikuchi and co-workers show that, in zebrafish, epicardial cells adopt only non-myocardial fates during heart development and also during heart regeneration, which is a naturally occurring process in adult zebrafish. The researchers identify the transcription factor gene tcf21 as a specific epicardial marker that is expressed throughout heart development and regeneration. Using tcf21 regulatory sequences and inducible Cre recombinase technology, they show that larval or adult cells labelled by tcf21 expression give rise to adult epicardial and perivascular cells during heart development and regeneration but do not differentiate into cardiomyocytes during either form of cardiogenesis. Thus, in zebrafish, natural epicardial fates are limited to non-myocardial cell types.

How PCP signalling directs neuronal migration

Planar cell polarity (PCP) signalling is implicated in the migration of facial branchiomotor (FBM) neurons during vertebrate brain development but how exactly does it function during this process? Cecilia Moens and colleagues now propose that PCP pathway components and a newly identified protein – Nance-Horan syndrome-like 1b (Nhsl1b) – have essential cell-autonomous functions during neuronal migration in zebrafish (see p. 3033). The researchers identify nhsl1b as a gene required for FBM neuron migration in a forward genetic screen. Nhsl1b localises to FBM neuron membrane protrusions, they report, and interacts with the PCP component Scribble (Scrib) to control FBM neuron migration. In cell transplantation experiments, they show that FBM neuron migration requires the cell-autonomous functions of Nhsl1b, Scrib and the PCP component Vangl2, in addition to the non-cell-autonomous roles of Scrib and Vangl2, which polarise the epithelial cells in the environment of the migrating neurons. The researchers propose, therefore, that Nhsl1b is a neuronal PCP effector that functions in migrating neurons to execute directed cell movements.

Plus…

The stem cell niche: lessons from the Drosophila testis

Tissue maintenance depends on stem cells that reside in specialized niches. Here, de Cuevas and Matunis review recent studies of the Drosophila testis and discuss how germline and somatic stem cells within this niche respond to local and systemic changes.

See the Review article on p. 2861

Development of the musculoskeletal system: meeting the neighbors

In March 2011, researchers met for the second Batsheva Seminar on Integrative Perspectives on the Development of the Musculoskeletal System. As reviewed by Gabrielle Kardon, the discussions at this meeting highlighted that interactions between the different tissue components are crucial for musculoskeletal morphogenesis.

See the Meeting Review on p. 2855

(1 votes)

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