Next week will see the 8th european zebrafish meeting happening in Barcelona, Spain. The Node will be there, and (if there is internet available) we will be tweeting from the conference using the hashtag #ezfish2013. So follow us on Twitter to find out what is happening! In addition, we have a group of Node zebrafish bloggers who will be reporting from the conference, so expect their meeting reports here on the Node.

If you are attending the conference, do look out for Cat. The Node will not have a stall, but Cat will be around, and is really looking forward to meet many zebrafish developmental biologists! You can see what Cat looks like in her introductory post. Looking forward to meet you there!

(4 votes)

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One of my favourite radio programs on the BBC is called Desert Island Discs. In this programme, a politician, activist, actor, writer or scientist is asked: if you had to live in a desert island, what would be the 8 records/songs that you would take with you? Although it is interesting to know what kind of music renowned people like, the music is really just an excuse. The reasons to choose each song are normally engrained in the interviewee’s life and achievements, and as such the music is just the starting point to a very personal and interesting interview. Desert Island Discs has been broadcast since 1942, and a vast proportion of the archive is available online to browse and enjoy. While perusing, I found that not only many known scientists have been interviewed, but a selection of those are well known developmental biologists. Here are some of the highlights:

– Martin Evans, Nobel Prize winner for his pioneering work on isolating and analysing embryonic stem cells

– John Sulston, Nobel Prize winner for his work on lineage analysis and programmed cell death in C. elegans

– Lewis Wolpert, known for his work on positional information in developmental biology, and for proposing the ‘french flag’ model of morphogen gradients.

If you want to know a little about the lives and experiences of these developmental biologists, then why not listen to the interviews? Many other scientists have been interviewed over the years (as well as many other interesting personalities) and you can access and search the full archive here.

(6 votes)

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Here are the highlights from the latest issue of Development.

Extrinsic cue for dendrite polarisation

Most neurons have a single axon on one side of their cell body and multiple dendrites on the opposite side. The establishment of this polarisation, which is essential for neuronal function, probably involves both intrinsic and extrinsic factors. Although several intrinsic factors have been identified, the identity of the in vivo extrinsic signals remains unclear. To remedy this situation, Sarah McFarlane and co-workers (p. 2933) have been studying dendrite polarisation in Xenopus retinal ganglion cells (RGCs). They report that neuropilin-1 and plexinA1, which form a holoreceptor for members of the axon guidance family of class III secreted semaphorins (Sema3s), are necessary to bias dendrite extension to the apical side of RGCs in vivo. They report that sema3a and sema3f are expressed on the basal and apical sides of the Xenopus RGC, respectively. Moreover, ectopically expressed Sema3s and inhibition of receptor signalling disrupt dendrite polarisation. The researchers suggest that neuropilin-1 and plexinA1 are co-receptors for an extrinsic cue, probably a Sema3, that directs RGC dendrite polarisation independent of axon polarisation.

Bi-polarity in tubulogenesis

Apico-basal polarisation is a crucial step in the formation of biological tubes. In model systems in which tubulogenesis occurs in cell clusters, the inner surface of each cell in the cluster differentiates into an apical domain where lumen secretion occurs, thus ensuring the formation of an unobstructed lumen. But in many developmental contexts, tubes form from simple cords of cells, which presents a unique challenge for the formation of a continuous lumen. On p. 2985, Di Jiang and colleagues investigate how this challenge is overcome during tubulogenesis in the Ciona intestinalis notochord, which is made up of a single file of geometrically identical cells. The researchers show that, during early tubulogenesis, a patch that contains the highly conserved Par complex and a set of tight junctions becomes established at both ends of the notochord cells. The formation of these two apical domains, they report, is controlled by Par3. Together, these results suggest a new mechanism for tubulogenesis from a simple cell cord that requires the formation of bi-apical cells.

Plants and animals converge to imprint

In mammals and plants, parental genomic imprinting, which results from mitotically stable epigenetic modifications, restricts the expression of specific loci to one parental allele. During gametogenesis in mammals, imprinting involves sex-dependent de novo DNA methylation and non-coding RNAs but does a comparable mechanism operate in plants? Here (p. 2953), Thiet Minh Vu, Frédéric Berger and colleagues report that de novo RNA-directed DNA methylation (RdDM), which depends on small interfering RNAs, regulates imprinting at several loci in Arabidopsis endosperm. By dissecting the expression of various members of the RdDM pathway, the researchers show that RdDM is required in somatic tissues to silence both parental alleles, whereas repression of RdDM in female gametes contributes to the activation of the maternal allele. Hence, both de novo DNA methylation and non-coding RNAs play a role in the regulation of imprinted loci in plants and mammals, which suggests that convergent evolutionary processes contribute to imprinting in these distinct groups of eukaryotes.

Rubbing out epigenetic marks in PGCs

During the migration of primordial germ cells (PGCs) to the genital ridge and during gonadal development, the stepwise erasure of DNA methylation and histone dimethylation marks ensures PGC totipotency and prevents the accumulation of epimutations. On p. 2892, Yoshiyuki Seki and co-workers explore the mechanisms underlying genome-wide epigenetic reprogramming in mouse PGCs by investigating the dynamics of epigenetic modifications in transposable elements. CpG methylation is markedly decreased in short interspersed nuclear elements (SINEs) in migrating PGCs, they report, but not in long interspersed nuclear elements (LINEs). By contrast, CpGs are rapidly demethylated in both SINEs and LINEs in gonadal PGCs. Four major factors that maintain DNA and histone methylation during DNA replication (and whose inhibition is associated with replication-dependent passive demethylation) are repressed at distinct stages of PGC development, they report, and DNA demethylation of transposable elements is disturbed in PGCs in which proliferation is impaired. These and other results suggest that PGCs use both active enzyme-catalysed DNA demethylation and passive demethylation for genome-wide epigenetic reprogramming.

Wnt signalling in early embryos

The Wnt signalling pathway is clearly required for gastrulation in mammalian embryos, but little is known about its extra-embryonic and preimplantation functions. Here (p. 2961), Janet Rossant and co-workers investigate the requirements for Wnt signalling in early mouse development using a mouse line that carries a floxed allele for the porcupine homolog (Porcn) gene. Porcn is required for the acylation and secretion of all 19 mammalian Wnt ligands, so Porcn function represents a bottleneck for Wnt signalling. Using zygotic, oocyte-specific and visceral endoderm-specific deletions of Porcn, the researchers show that Porcn-dependent Wnt signalling is not required for preimplantation development or for implantation itself, and they confirm that gastrulation is the first Porcn/Wnt-dependent event in embryonic tissues. They also identify chorio-allantoic fusion as the first major Porcn/Wnt-dependent event in extra-embryonic tissues. Together, these findings show that, although Porcn-dependent Wnt signalling is important for embryonic and placental function, it does not have an essential role in preimplantation development or in blastocyst lineage specification.

Gpr125 helps set gastrulation in motion

During vertebrate gastrulation, polarised cell behaviours orchestrated by Wnt/planar cell polarity (PCP) signalling drive the convergence and extension (C&E) movements that elongate the embryo. Xin Li, Florence Marlow, Lilianna Solnica-Krezel and colleagues now identify Gpr125, an adhesion G protein-coupled receptor, as a novel modulator of Wnt/PCP signalling during gastrulation in zebrafish embryos (p. 3028). The researchers show that overexpression of Gpr125 impairs C&E movements in zebrafish embryos and that reduced Gpr125 function exacerbates the C&E defects and the facial branchiomotor neuron migration defects seen in embryos with reduced Wnt/PCP signalling. Gpr125 directly interacts with Dishevelled (Dvl), they report, and recruits Dvl to the cell membrane, a prerequisite for Wnt/PCP activation. Finally, they show that Gpr125 and Dvl mutually redistribute into discrete membrane subdomains and recruit a subset of PCP components into membrane subdomains. Thus, the researchers suggest, Gpr125 might act as a component of PCP membrane complexes and as a modulator of Wnt/PCP signalling in vertebrates.

Plus…

Tubulogenesis

In this  poster, Luisa Iruela-Arispe and Greg Beitel summarise our current understanding of the various processes by which tubes form during development, and the cellular and molecular mechanisms underlying tubulogenesis.

See the Development at a Glance article on p. 2851

Oct transcription factors in development and stem cells: insights and mechanisms

Oct proteins play varied and essential roles during development. Here, Dean Tantin outlines our current understanding of Oct proteins and the regulatory mechanisms that govern their role.

See the Primer article on p. 2857

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Developmental biology from near the south pole

Kia Ora from New Zealand

Hi, I’m Megan Wilson and I’m a lecturer in the Department of Anatomy at the University of Otago, Dunedin, New Zealand. My research focus, and my scientific passion, is developmental biology. In this new regular blog on the Node, I hope to bring NZ developmental biology to the rest of the world. The NZ developmental biology community is vibrant and diverse, and overlaps with a range of other disciplines, from medical research to evolution and ecology.

It wasn’t always the case, though.  As a Biochemistry undergrad, and then a PhD student at Otago in the late 1990s, there were very few options for studying developmental biology. My interest in developmental biology came from wanting to know more about the genetic disorder my brother had, Tuberous Sclerosis Complex (TSC). TSC affects multiple organ systems, but particularly the kidney, brain and skin, causing benign tumors to grow.  I wondered why these tumors occurred in only a few organs and why symptoms varied so much between individuals.  In order to really understand the origin of this disorder, I had to learn a little developmental biology, became fascinated by it, and this sparked a career shift.  After a postdoc with Prof Peter Koopman in the Institute for Molecular Bioscience in Brisbane, I returned to Otago to work as a Research Fellow with A/Prof Peter Dearden in Biochemistry, before establishing my own lab in the Anatomy Department at Otago in 2010.

Otago University is located in the lower half of the South Island in Dunedin, New Zealand.  It was the first University in New Zealand (founded in 1869) and now boasts a student population of over 20,000 and teaching/research campuses in Wellington and Christchurch as well as Dunedin.  It is very much a ‘research-led’ institution with most teaching academics also running active research groups. Developmental biology at Otago is by nature multidisciplinary and multidepartmental –  researchers from the departments of Anatomy, Biochemistry, Medicine, Zoology and Pathlogy contribute to teaching popular 3rd and 4th year courses on development.  At Otago there has a been a steady growth in developmental biology research over the past 10-15 years, to the point where today there are more than 10 independent research labs at Otago University, including my own http://wilsonlab.otago.ac.nz.  Developmental biology research at Otago covers a full range of animal and plant systems including mammals, insects, amphibians, urochordates, Arabidopsis and humans.

Why post about NZ developmental biology research?

Well, while NZ is a wonderful place to live and we have all the tools and talent to perform cutting-edge research, it’s true that we are very very far from everyone else.  To get to a conference in the US or Europe, requires up to 36 hours in a plane (or more often many planes) and several thousand dollars in travel funds. As a result, many of us only get to one international meeting a year, and very rarely to smaller more focused meetings.  This makes it very difficult to network, set up new collaborations or present our science to a wider audience.  So the next best thing is to make use of social media such as blogging to share with everyone some of the exciting work being carried out in New Zealand, which is what I hope to do here.

So in coming posts here at the Node I will profile some of the leading researchers at Otago and elsewhere in New Zealand.  I will also provide meeting reports from local conferences from this side of the world. If you have any thoughts or comments, email me on meganj.wilson@otago.ac.nz.

(13 votes)

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June saw a lot of interesting posts on the Node! Meeting reports, research posts, and more, as well as few new jobs in our jobs page. Here are some of the highlights:

Meeting reports

Several meetings were covered on the Node this month:

• – Harry attended the International Society for Stem Cell Research (ISSCR) annual meeting in Boston, and posted a series of reports on the meeting
• – The Node was at the International Society of Development Biology (ISDB) in Cancun, and posted daily updates.
• – Rachael attended the satellite symposium on left-right asymmetry that preceded the ISDB, and wrote a post on her highlights.

Research Highlights

– Kif Liakath-Ali highlighted two recent papers that used insects as an inspiration to develop new technologies.

– Cantas discussed his recent paper on the formation of the primitive streak and the induction of mesoderm.

– And Albert described how he applied the brainbow technique to zebrafish.

Woods Hole embryology course

This year’s Woods Hole embryology course is underway, and Lara wrote a post about her impressions on the first few weeks of the course. We also had another round of beautiful images from last year’s course up for voting, and the big winner this time was a skeleton preparation of a pig embryo. This winning image will feature in the cover of Development in a coming issue.

Also on the Node: 

– Kara wrote a personal account of how she returned to the bench after working as a journal editor, showing that leaving academia doesn’t necessarily mean that you can’t come back.

– And Erin’s stem cell image blog focused on a recent paper on retinal regeneration.

Happy Reading!

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Just before the ISDB meeting in Mexico, over a hundred researchers gathered for a satellite symposium on the development of left-right asymmetry. Although the external body plans of vertebrates (and many invertebrates) are bilaterally symmetrical, various internal organs are positioned asymmetrically. For example, the heart is located towards the left, but paired organs such as the lungs are also asymmetrical, as the left lung has fewer lobes than the right in order to make space for the heart on that side of the body. Correct development of the left-right axis is vital for all organs to be packaged properly within the body cavity, so left-right defects often have disease implications.

The symposium began by looking at left-right patterning in some of our more distant relatives: flies, nematodes, polychaete worms, limpets, sea squirts and sea urchins.

Bill Wood used a nice visualisation to describe left-right asymmetry in the early C. elegans embryo, telling us to imagine the one-cell embryo as a cylinder with the M.C. Escher artwork ‘Bird Fish’ wrapped around it. As the embryo prepares for its first cell division into anterior and posterior cells, there is an off-axis deformation of the cortical network that stretches the birds and fish so that they are longer and thinner on one side of the cylinder. This means that the birds and fish on the other side are pulled in the opposite direction and become shorter and fatter, creating a difference between the future left and right sides of the body during the very first cell division. ‘Bird Fish’ seemed an appropriate choice of pattern to demonstrate this point as the model organisms representing these two groups, chick and zebrafish, use very different mechanisms to establish left-right asymmetry and would be discussed later in the meeting…

We then moved on to vertebrate systems with talks describing the events taking place at the node of mouse and its analogous structures in other animals, where motile cilia generate leftward fluid flow. Dominic Norris proposed a mechanism for the detection of this flow, which initiates a Nodal signal on the left side of the body, while Chris Wright and Jose Antonio Belo talked about the dynamics of Nodal ligands and antagonists, respectively.

A recurrent debate was the role of early determinants of asymmetry, and how these might work with the cilia-mediated mechanism seen in many, but not all vertebrates. Martin Blum proposed a model to accommodate both processes and discussed their possible evolutionary relationships. The frequently mentioned ‘problem’ with a cilia-based strategy is that some animals establish the left-right axis without cilia, such as the chick. Leonor Saude described the asymmetry created by the leftward movement of cells around Hensen’s node and the termination of this process by a cell adhesion mechanism.

The early differences between the left and right sides of the body must be translated into an effect on organogenesis later in development. This was addressed by Rebecca Burdine who showed that the Nodal signal increases cell movement on the left side of the zebrafish heart tube to facilitate its leftward jog, and Nanette Nascone-Yoder who has been investigating the role of the left-specific transcription factor Pitx2 in asymmetric gut curvature in frogs.

Even organs that appear symmetrical in their gross morphology can be asymmetrical; the brain exhibits many functional asymmetries. Steve Wilson has utilised the optical clarity of zebrafish to visualise asymmetric connections in the brain and asymmetric activity in response to stimuli, while Marnie Halpern described some ways in which reversed brain asymmetry can affect fish behaviour.

In contrast to the talks on asymmetry, Olivier Pourquie explained how symmetrical structures such as the somites overcome the differences between the left and right sides of the body to maintain their symmetry during development.

The medical relevance of left-right axis development was summed up by talks on diseases associated with asymmetry defects; Cecilia Lo described her work on congenital heart disease and Zhaoxia Sun spoke about primary ciliary dyskinesia. Research into left-right asymmetry has even inspired a recent article in the New York Times, so a developmental process that has fascinated scientists for decades has infiltrated popular culture too – it must be important!

(3 votes)

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Another set of beautiful images, and another great winner! The winner of this year’s 3rd round of the Woods Hole Embryology Course is the pig embryo!

This great picture was taken by Marina Venero Galanternik (University of Utah), Rodrigo G. Arzate-Mejía (Universidad Nacional Autonoma de Mexico), Jennifer McKey (Universite Montpellier) and William Munoz (The University of Texas MD Anderson Cancer Center). It shows a colour inverted image of a skeleton preparation of a pig (Sus scrofa domesticus) embryo.

The runners-up to this competition were the Drosophila embryos by Davon Callander (Oregon State University); a fluorescently stained annelid by Eduardo Zattara (University of Maryland, College Park); and a grafted Xenopus by Elsie Place (MRC National Institute of Medical Research).

This beautiful pig embryo will feature in the cover of Development in a coming issue. As for the cover competition, there is still one round of beautiful pictures to come this year!

(2 votes)

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We’ve all heard the aphorism that once you leave academia, you can’t go back. A little over two years ago, I wrote about my transition from academic research to scientific editing. Now, after completing my first year as an assistant professor of Biology at Reed College, I’m offering proof that lane changes, U-turns, and detours can lead you back to the ivory tower. Many people suggested that I wouldn’t be able to come back to academia when I chose to accept an editorial job at Cell, and I had every intention of sticking with my chosen path of scientific editing. After almost a year of sitting at a desk in an office that didn’t smell like acetic acid or freshly poured LB agar, a niggling feeling kept telling me that something wasn’t quite right. A few soul-searching diary entries, a couple of personality type indicators, and many conversations with friends and mentors helped me discern exactly what that feeling was trying to tell me. Scientific careers can follow many different trajectories and sometimes the “best fit” path is not always the easiest or most logical choice.

It is my hope that sharing my journey thus far helps scientists at all stages of their careers recognize that many valid career paths exist and that lane changes, U-turns, and detours are always possible. And I hope that this piece will spark conversation, here and elsewhere, about the varied and multiple careers scientists pursue.

The exit ramp
When I made the decision to leave my post-doc for the position at Cell, I focused on what the job offered: the ability to do more of what I liked – thinking and communicating science – and less of what I didn’t like – worrying about funding and dealing with the pressure to publish in high-impact journals. (The irony of working at a high-impact journal was not lost on me.) Plus the editorial job put me in the same time zone as the rest of my family. It was a logical and rational decision.

The novelty of scientific editing excited me in a way that my day-to-day work as a post-doc didn’t and, as a result, I disregarded the things that I actually enjoyed about working in academia, like the experimental troubleshooting, the microscopy, the competition to figure something out before someone else, the pipetting, the interactions with students. Working as an editor helped me hone my critical thinking skills, gave me a strong foundation in written communication, and also helped me clarify who I was, what I wanted, and what I valued. I need to make (or at least feel like I’m making) unique and creative contributions to science.

Lost without a map
In an era of tight funding and high-stakes research, my decision to leave a very good and relatively secure job for one fraught with stress and insecurity might seem a little odd, and certainly not very practical. It is, in fact, one of the least rational decisions I’ve made. And although we scientists are often known for our logic and careful reasoning, many of us are intuitive thinkers, making decisions based, at least partly, on gut instinct. This is not to say that I did not enjoy my time as an editor, because I did. I count myself incredibly fortunate to have worked as a scientific editor at Cell, and had my academic job search been unsuccessful, I’d still be handling manuscripts, recruiting papers, talking with authors, attending meetings as an editor, and savoring the opportunity to read papers and work with really smart people.

The U-turn…
Applying for assistant professorships while also working as a full-time editor forced me to focus on exactly what I wanted. While many of my post-doc friends and colleagues indiscriminately applied to 30 or 40 positions, I applied to seven. I was mindful of location (after living in a variety of places up and down the East Coast and in London, my husband and I wanted a place that had plenty of green space and the option to cycle and walk most places). I knew from multiple experiences that I wanted to work directly with undergraduate students and maintain a small, active research program. My weekends were dedicated to outlining my tentative research program and customizing my application materials for each position on my list. My scientific “U-turn” was possible, in large part, because of an incredibly generous post-doc mentor (Steve Wilson at UCL) who allowed me to resume some of the projects I’d left behind and use them as a jumping off point for my long-term research program.

The new path…
I’m not quite sure what the various search committees saw in my application, but I was extremely fortunate to have two fantastic offers to teach and do research at top-notch liberal arts schools. I love my current job at Reed College. My experiences as a high school science teacher (before grad school) and a scientific editor (before this position) endowed me with a unique and useful skillset. As a professor at small liberal arts college, I relish designing both curriculum and experiments. I enjoy reading, writing, and inviting notable scientist for seminars. I impact the future of science by teaching and mentoring undergraduates in my lab. I’ve embraced the academic lifestyle. And although our recently adopted dog, Mickey, would like to think his need for a run is what gets me up bright and early ~5am, it’s really the opportunity to share my love of research, encourage students to explore and experiment, and mentor budding scientists that get me out of bed every morning. The life of an assistant biology professor at a place like Reed can be incredibly rewarding, but it also comes with a healthy dose of stress. Fear of delivering a subpar lecture, apprehension about lab activities not working, and anxiety about my nascent research program certainly gave me some grey hairs. That said, I wouldn’t have traded this past year for anything (well, maybe more sleep). I’ve never learned as much, slept as little, worried as much, or felt as happy as I have this past year. And I wouldn’t have survived this year without the stress relief and support that my dog, husband, wonderful colleagues, mentors, and friends provided.

Even if Reed isn’t my final academic home, my journey so far has taught me to seize the opportunities that come my way, to learn and live as fully as I possibly can. And I hope that this one example of leaving and returning to academia gives you the courage to search for the career path that is right for you.

What are your experiences? Have you found your “dream job”? What have you learned from taking one of the less mainstream career paths? Please post here to continue this exploration of career trajectories.

(46 votes)

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We invite applications for a postdoctoral research fellow to join the lab of “Imaging and Regulation of Morphogenesis in Higher Vertebrates” at the Pasteur Institute in Paris, France. Our lab is interested in understanding the  morphogenesis of developing structures, at a cellular level. Using avian models we combine state-of-the-art live imaging methodologies, quantitative analyses, biophysical, cellular and molecular biology approaches to access the cellular dynamics of development.

This specific project aims at elucidating the cellular events underlying the initiation of limb bud formation and how such cell events are dynamically regulated at the molecular level. For more information about projects and the lab please visit: www.jgroslab.com .
The position is a two-year postdoctoral position funded by the FRM (Fondation pour la Recherche Medicale) available immediately, although the starting date is flexible. We are seeking highly motivated candidates with expertise in developmental and/or cellular biology. Experience in imaging will be positively considered.

The Pasteur Institute, located in the vibrant city of Paris, has a longstanding history of excellence in developmental biology and in science in general, with access to excellent core facilities.

Applicants should send a cover letter (describing briefly research interests), a C.V and contact information for up to 3 academic references to jgros@pasteur.fr.

Postdoc_Ad_Institut_Pasteur

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After two weeks of intense work in the Woods Hole MBL Embryology course, I am beginning to understand why this course compels TAs, faculty and students from around the world to return year after year. The 24 students in the 2013 Embryology class work on a diverse set of organisms including worms, mice, chick, coral, dinosaurs, and lophotrochozoans, but we are tied together by our interest in development.

Our desire to understand development brought us to this six-week course featuring daily lectures, discussion and many hours of work in the lab with a variety of model systems. It is intense work, but at the same time, it’s all play. In the last two weeks together, we’ve studied how sea urchin, nematode, and arthropod eggs turn into swimming or crawling larvae. Adding sea urchin eggs and sperm together, we watched the vitelline envelope balloon indicating fertilization. Timelapse movies captured cell divisions, gastrulation, filopodial dynamics, and organ development. With confocal microscopes, we examined localization of proteins and RNAs to understand patterning and created 3D reconstructions of embryos.

The most striking thing to me about the MBL has been not the plethora of embryos or the microscopes, but the community of scientists it builds. The course directors and many of the speakers were students of the course, with stories and fond recollections. The faculty, course directors, and TAs worked with us all day and most of the night, troubleshooting microscopes or antibody staining and providing a wealth of experience and knowledge. As a student, I have the privilege of being a part of this community, working where many scientists, including T. H. Morgan, did their summer research. Much of the rich heritage of the MBL is showcased in the WHOI library rare books room, which features Morgan’s traveling microscope, multiple Nobel prizes, and scientific texts dating back to the 1500’s.

Our time at Woods Hole so far has already changed how we look at the world. You approach murky seawater with fascination, because you will find fish and snail embryos. I look at my research with a broader perspective and am excited to discover unexpected connections between my work and my classmates’ research.  You are confident enough to tackle new techniques and ask questions boldly; to gain experience through work and interactions with faculty. I can’t wait to see what the next four weeks hold.

(7 votes)

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