In 1999, twenty-nine planarians, courtesy of Dr. Maria Pala made the journey across the Atlantic from the beautiful mediterranean island of Sardinia, to Baltimore, Maryland, into the hands of my advisor, Phil Newmark, who was then a post-doctoral fellow in Alejandro Sánchez Alvarado’s laboratory at the Carnegie Institution of Washington.

Realizing the potential of the flatworms he held in his hands, he took advantage of their power of regeneration and cut them into many pieces, each of which grew into a whole new animal. In this way, he generated clonal lines of the sexual strain of the planarian Schmidtea mediterranea. These animals are simultaneous hermaphrodites- meaning that they have functional male and female reproductive organs; unlike C. elegans, they are not self-fertile and must mate to propagate. Inbred lines were derived in the Sánchez Alvarado lab from one of the clones and used for sequencing the S. mediterranea genome.

When I joined the Newmark lab at the University of Illinois at Urbana-Champaign, I was fascinated by the developmental plasticity of these planarians. Due to a population of stem cells called neoblasts, they can grow and degrow, and their reproductive system can regress and regrow depending on environmental factors. Even more amazing, these flatworms could regenerate their whole reproductive system, including the germ line, from fragments that were initially devoid of reproductive tissue. Understanding the mechanisms that the planarians use to achieve this feat is one of the main themes of research in the Newmark Lab.

Interestingly, there is a strain of S. mediterranea that reproduces asexually by transverse fission. The existence of two divergent modes of reproduction in a single species presents a unique opportunity to identify conserved and species-specific genes that are important for germ cell development and reproductive system maturation.

Together with my colleagues, Yuying Wang and Joel Stary, we performed microarray analyses to identify genes that are expressed differentially between the asexual and sexual planarians; we then used in situ hybridization to examine the cell types in which these genes were expressed. To complement this transcriptomic approach, we also identified several antibodies and fluorescent lectin-conjugates that labeled components of the planarian reproductive system.

This work, as presented in our BMC Developmental Biology paper, provides markers and tools to further characterize the hermaphroditic reproductive system of S. mediterranea. I was thrilled to see that there were genes specific to either male or female components of the reproductive system, suggesting sex-specific mechanisms in a simultaneous hermaphrodite. I am very excited to unravel the mystery of how these hermaphroditic worms are able to develop both male and female parts. With their genome now experimentally accessible, little did the twenty-nine planarians know how they would contribute to science when they made their journey across the Atlantic 13 years ago.

(11 votes)

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

Neural circuit building

During development, sensory neurons form neural circuits with motoneurons. Although the anatomical details of these circuits are well described, less is known about the molecular mechanisms underlying their formation. To investigate the involvement of motoneurons in sensory neuron development, Hirohide Takebayashi and colleagues analyse sensory neuron phenotypes in the dorsal root ganglia (DRG) of Olig2 knockout mouse embryos, which lack motoneurons (see p. 1125). These embryos, they report, also have reduced numbers of sensory neurons but increased numbers of apoptotic cells in the DRG. In addition, the axonal projections of the sensory neurons in these embryos are abnormal. Because neurotrophin 3 (Ntf3) and its receptors are strongly expressed in motoneurons and sensory neurons, respectively, the researchers also investigate whether Ntf3 is one of the motoneuron-derived factors that regulate sensory neuron development. Notably, the sensory neuron phenotypes in Ntf3 conditional knockout embryos resemble those observed in Olig2 knockout embryos. Thus, the researchers propose, motoneuron-derived Ntf3 is a pre-target neurotrophin that is essential for survival and axonal projection of sensory neurons.

SIK3 bones up on chondrocyte hypertrophy

Most vertebrate bones develop through endochondral ossification. During this process, proliferating chondrocytes form a cartilage scaffold, differentiate into hypertrophic chondrocytes and die. The cartilage scaffold is then degraded and replaced by bone. Chondrocyte hypertrophy is, therefore, crucial for endochondral ossification. On p. 1153, Noriyuki Tsumaki and colleagues identify salt-inducible kinase 3 (SIK3) as an essential factor for chondrocyte hypertrophy in mice. SIK3-deficient mice, the researchers report, exhibit dwarfism, bone malformation and accumulation of chondrocytes in various bones. These phenotypes, they suggest, are due to impaired chondrocyte hypertrophy. Consistent with this suggestion, SIK3 is expressed in prehypertrophic and hypertrophic chondrocytes in the embryonic bones and postnatal growth plates of wild-type mice. Other experiments show that SIK3 anchors histone deacetylase 4 (HDAC4) in the cytoplasm, thereby releasing MEF2C, a transcription factor that facilitates chondrocyte hypertrophy, from suppression by HDAC4 in the nucleus. These results suggest that the regulation of HDAC4 by SIK3 is important for the progression of chondrocyte hypertrophy during skeletal development.

PRMT5 and stem cell function

Stem cells are essential for growth, development, gamete production and tissue homeostasis but what regulates their maintenance and function in vivo? On p. 1083, Phillip Newmark and colleagues report that the conserved protein arginine methyltransferase PRMT5 promotes stem cell function in planarian flatworms. These organisms contain a population of adult stem cells called neoblasts that can regenerate all the worm’s tissues. Neoblasts characteristically contain chromatoid bodies, large cytoplasmic ribonucleoprotein (RNP) granules similar to structures that are present in the germline of many organisms. The researchers show that, like germline RNP granules, chromatoid bodies contain proteins bearing symmetrical dimethylarginine (sDMA) modifications, probably including the PIWI family member SMEDWI-3. PRMT5 is responsible for sDMA modification of these proteins, they report, and PRMT5 depletion results in fewer chromatoid bodies, fewer neoblasts, and defects in regeneration, growth and homeostasis. Together, these results identify new chromatoid body components that are involved in neoblast function and add to the evidence that suggests that sDMA modification of proteins stabilises RNP granules.

BR(in)G1 on male meiosis

Mammalian germ cell development and gametogenesis involve several genome-wide changes in epigenetic modifications and chromatin structure. Here (p. 1133), Terry Magnuson and co-workers explore the role of the mammalian SWI/SNF chromatin-remodelling complex during spermatogenesis in mice. The researchers report that levels of the SWI/SNF catalytic subunit brahma-related gene 1 (BRG1) peak during the early stages of meiosis. Consistent with this expression pattern, germline ablation of Brg1 produces germ cells that arrest during prophase 1, the stage of meiosis during which the induction and repair of DNA double-strand breaks generates recombination between homologous chromosomes. In line with the timing of their meiotic arrest, BRG1-depleted spermatocytes accumulate unrepaired DNA and fail to complete synapsis. They also exhibit global alterations to histone modifications and chromatin structure, including alterations that are associated with DNA damage and heterochromatin. The researchers propose, therefore, that BRG1 has an essential role in spermatogenesis and that BRG1-containing complexes function in the programmed recombination and repair events that occur during meiosis.

Binary route to (non)-neural competence

During gastrulation, neural crest and cranial placodes originate at the neural plate border and from an adjacent territory, respectively. But do these ectodermal tissues arise from a common precursor or from neural and non-neural ectoderm (the binary competence model)? On p. 1175, Gerhard Schlosser and colleagues use tissue grafting in Xenopus embryos to tackle this controversy. They show that, at neural plate stages, competence for induction of neural plate, border and crest markers is restricted to neural ectoderm, whereas competence for induction of panplacodal markers is confined to non-neural ectoderm. The homeobox protein Dlx3 and the transcription factor GATA2 are both required cell-autonomously for panplacodal and epidermal marker expression in non-neural ectoderm, they report. Moreover, the ectopic expression of Dlx3 (but not GATA2) in the neural plate is sufficient to induce non-neural markers, whereas the overexpression of Dlx3 or GATA2 suppresses neural plate, border and crest markers in the neural plate. Together, these results support the binary competence model and implicate Dlx3 in the regulation of non-neural competence.

Morphogen-based simulation of fin development

One of the greatest challenges in developmental biology is to understand how shape and size are controlled during development. Interactions between growth and pattern formation mechanisms are key drivers of morphogenesis but are difficult to study experimentally because of the highly dynamic nature of development in space and time. Here (p. 1188), Anne-Gaëlle Rolland-Lagan and co-workers use simulation modelling to explore how mobile signals, such as morphogens, might coordinate growth and patterning during zebrafish caudal fin development and regeneration. The zebrafish fin comprises 16 to 18 bony rays, each of which contains multiple joints along its proximodistal axis that give rise to segments. The researchers propose a model in which the interaction of three postulated morphogens can account for the available experimental data on fin growth and joint patterning and for the regeneration of a properly shaped fin following amputation. This simple, plausible model provides a theoretical framework that could guide future searches for the molecular regulators of fin growth and regeneration.

Plus…

CTCF: insights into insulator function during development

The nuclear protein CTCF when bound to insulator sequences can prevent undesirable crosstalk between genomic regions and can shield genes from enhancer function. Here, Rainer Renkawitz and colleagues discuss the mechanisms underlying developmentally regulated CTCFdependent transcription. See the Primer on p. 1045

The hypoblast (visceral endoderm): an evo-devo perspective

Claudio Stern and Karen Downs discuss the function and evolution of the chick hypoblast and the visceral endoderm in mouse, highlighting the common roles played by these tissues. See the Review on p. 1059

(No Ratings Yet)

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After the devastating earthquake last year forced us to cancel the chick meeting, we are happy to announce that the next chick meeting will be held in Nagoya, Japan. The meeting will be held from 14th to 18th November 2012.

Please check the website for further details.

(6 votes)

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My inbox is full of abstract submission deadline reminders and meeting registration announcements, so I thought I’d share a few. Which conferences are you planning to go to this year?

Abstract submission deadlines:
* February 21 (tomorrow!) – Abstract submission deadline for the JSDB/JSCB meeting (May 28-31, Kobe)
* March 2 – Abstract submission deadline for the BSDB/BSCB/JSDB meeting (April 15-18, Warwick)
* March 26 – Abstract submission deadline for the SDB Meeting (July 19-23, Montreal)

Registration open:
* The International Conference on Zebrafish Development and Genetics (June 20-24, Madison, Wisconsin) just opened abstract submission. Get yours in by March 27. Meeting registration starts later this week.
* The Santa Cruz Developmental Biology Meeting (August 8-11, Santa Cruz) launched their website and Facebook page. Abstract submission and registration will open later this Spring.

(No Ratings Yet)

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At the start of February, EuroStemCell used our Twitter page @eurostemcell in a new way: We posted a series of fascinating facts and ‘test your knowledge’ questions about stem cells, using the hashtag #stemcellfacts. The tweets covered a lot of ground, from embryonic stem cells and blastocysts to skin stem cells, gut stem cells, heart cells and regeneration.

Thanks to Kate Blair for developing the #stemcellfacts concept and researching the content for the 30 tweets. You can see all the tweets collated with responses from other tweeters in our Storify summary.

We’ve got off to a flying start in 2012 with lots of other activities too – new blogs, translation into Italian, new educational tools and articles about embryonic stem cells. Find out more in our February newsletter. And as ever, we’re keen to hear you feedback at www.eurostemcell.org/contact.

(4 votes)

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Cambridge University Research has recently launched a series of videos called “Under The Microscope”, that showcase some of the microscopic research carried out at the university. Two of the eight videos they’ve published so far have featured developmental biology:

PhD student Matt Benton talking about beetle development.

Research fellow Erica Watson describes mouse development.

The “Under the Microscope” videos are meant for a wider audience, and it’s interesting to read some of the comments the videos get on YouTube, from people who are sometimes only thinking about development for the first time. But I thought even the seasoned developmental biologist might enjoy having a look at them.

Find all the videos on their video and audio page.

(7 votes)

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Last June, Eva summarised the Node’s alternative careers stories, personal accounts of how scientists made their transitions from research into various alternative career paths. As a friend of Andrea Hutterer, who is now the Fellowships Manager at EMBO, I witnessed her exciting leap from the bench into science management back in 2010, and now asked her to tell her story. I’m sure her experiences will interest the Node’s readers and complement the alternative careers stories already available on the site. Enjoy the interview!

Briefly tell us about your scientific career.

I studied biochemistry in Vienna and then did both my diploma thesis and my PhD in Jürgen Knoblich‘s lab at IMP and IMBA in Vienna. The focus of my thesis was asymmetric cell division in the nervous system of Drosophila. After that I joined Masanori Mishima‘s group at the Gurdon Institute in Cambridge, UK, for a postdoc. In his lab, I studied the process of cytokinesis.

Why did you quit research?

I was simply not sufficiently fascinated by one particular biological problem. My CV was good in scientific terms, so I think I could have gone ahead and started to apply for PI positions. But without being passionate about a question I think it’s hard to be successful, and being quite ambitious I decided it’s not the right career path for me.

What got you interested in research funding and policy? Did you consider other career paths?

Once I had decided to look into alternative careers, I needed to find out which career paths were open to me. I looked into loads of things – management consulting, scientific editing, medical writing, conference organising and science communication. In the end it was clear that science management was the best choice for me, as I would still have direct contact to scientists and thereby get a broad overview of scientific progress and emerging fields. On top of that, one can make a difference in terms of policy, for example by dealing with researchers’ employment conditions or gender issues.

Did you take any additional courses to polish your CV?

At the Gurdon Institute I was lucky enough to be able to take advantage of the fantastic careers service Cambridge University offers. In the beginning, I almost randomly took courses such as microeconomics, web-authoring and programming languages. This helped in a way that I found out quickly that pure economics were not entirely my thing and Perl was not my language. Other courses were more useful, for example when I learned the basics of using HTML to build websites or how to best write a CV for non-scientific jobs.

With regard to “polishing” my CV, it wasn’t so much the courses I listed but more how I organised the CV. I tried to emphasise my soft skills and highlighted extracurricular activities such as supervising younger students and organising retreats and symposia.

How easy was it to get your first job in funding?

It wasn’t easy at all, not even to get interviews. My scientific CV was good, but I had virtually no other relevant experience. Many employers appreciate even the smallest amount of experience more than a fantastic scientific CV, so what you really need when coming out of a PhD or postdoc is to get a foot in the door.

The first interview I got was with Cancer Research UK, but they didn’t offer me the job. I then got offered a job as Science Manager with the Medical Research Council (MRC) in Swindon, UK. I was quite over-qualified for this job since it didn’t even require a PhD, plus it came with a significant pay cut, but I was glad to have been offered it and accepted. In hindsight, it was the perfect stepping stone.

As preparation for the interviews, the Cambridge Careers Service again proved extremely helpful, because they offered mock interviews with the career advisor. It helped immensely to practise – I found out what I might be asked in an interview and I learned to explore different possibilities for answering these questions. I simply got an idea of what to expect during the process.

What does your work consist of?

On an everyday basis, I do some general administration, the details of which depend on the various fellowship application deadlines: I read proposals, find referees, talk to fellows, talk to my team [Andrea has three administrative staff to manage] and attend in-house management meetings. Every now and then I travel to career events to give talks about the programme, or attend workshops somewhere in Europe, which cover different aspects that come with the programme, such as a recent workshop on tracking research careers.

I also write grant proposals to try to get more money for the programme, and organise and attend the EMBO Fellows’ meetings in Heidelberg and the US. So it’s a very diverse job and I’m never even remotely bored!

Is there anything you miss about working in research?

At the MRC, although my colleagues were great I sometimes missed the international environment, which I do have here at EMBO. Sometimes I also miss standing at the bench, running around in the lab, being physically active. But I’m aware that that would have stopped sooner or later even if I had stayed in research and had become a PI.

What advice do you have for PhD students and postdocs wanting to leave academic research?

Find out why exactly you want to leave and what you would rather do. Even if you’re unclear whether research might be the right thing for you or not, start thinking about alternatives and get involved in non-scientific activities early on. There’s actually quite a lot one can do with our education. You just need to be clear about your goals, have a good non-scientific CV ready and work towards the new career profile. It might take a while until you get the job you have in mind, and you possibly need to be prepared to take pay cuts and will maybe feel slightly under-challenged in your first non-research job, but at least for me it was all worth it.

(14 votes)

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The ability to learn and form memories are cognitive functions associated with the brains ability to produce and co-ordinate new neurons effectively. These cognitive abilities are well known to degenerate with age due to diminishing neurogenesis. This study published in Nature, shows that reduced regenerative ability of the brain is due not only to intrinsic cues from the central nervous system, but also extrinsic blood-borne cues communicating with the neurogenic niche via closely surrounding blood vessels. This investigation aimed to find molecular differences in the systemic environment of ageing mice using a heterochronic parabiosis study to identify a correlation between blood-borne factors and neurogenic decline.

To address this, young mice (3-4 months) were exposed to the systemic environment of old mice (18-20 months). This was achieved by the intravenous injection of plasma obtained from an old mouse into a young mouse. The change in systemic environment produced mice with deficient synapse plasticity and reduced cognitive functions such as learning and memory. Proteomic analysis comparing the plasma of young and old mice revealed a correlation between ageing and a group of chemokines. Of particular interest was the chemokine CCL11 which has not been linked previously with ageing. Administration of CCL11 by intraperitoneal injection caused a reduction in adult mouse neurogenesis and in turn these mice demonstrated impaired learning and memory. Further investigation showed this chemokine to increase in an age dependent manner in human plasma and cerebrospinal fluid indicating similarity in age related systemic content across species.

Could the molecular content of our systemic environment be responsible for the neurogenic signs of ageing? This study gives convincing evidence for a link between certain age related blood-borne factors with diminishing neurogensis and cognitive function associated with ageing. The converse to this study is of course, what pro-neurogenic factors may be present in the systemic milieu. These could have potential in future therapy for age related neurogenic disorders.

The full paper can be found by following this link

http://www.nature.com/nature/journal/v477/n7362/full/nature10357.html

(5 votes)

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Dear Developmental biology community,

I would like to bring to your attention a potentially valuable resource for your teaching and research endeavors.  I am a neurodevelopmental biologist at Smith College.  I started teaching a course in Developmental Biology back in 2005, and since then have been utilizing web conferencing technology to bring the research behind concepts alive in the classroom.  My students have been interacting with leading scientists in the field of developmental biology holding organized Q&A video conferences focused on current and seminal research articles.  I am posting this to the Node as since I started using this pedagogical approach I have been recording these discussions, and with full consent provided, I have established an online repository of these recordings via my lab website.  I have each conference (40 now and growing) organized by topic for ease of searching, and each individual session is further broken down by specific question to facilitate quick access to your greatest interest.

Because these sessions are based on key research papers they are extremely applicable for any teacher or student to use in their own courses as supplemental resources to what is probably the very same topics being covered.  For instance, I often assign my students select conferences to watch to supplement their readings or coverage of the material.  Moreover, in class I will poise certain questions about a topic to my student and after some discussion, click on say, Dr. Cliff Tabin’s response to the similar question.  It provides a new and real perspective to the information that students truly appreciate and fosters long-term retention of the material.

There are also many other positive outcomes to both conducting and watching these conferences.  Namely students gain a very different and revealing perspective of not only where a particular field of Dev Bio is moving, but more personal understandings of who the scientists are and how they got to where they are today.  Listening to these remarkable scientists articulate their thinking process to address the research question is extremely illuminating to the developing scientist in your classroom.

So I invite and encourage you to check out these discussions as I am disseminating them for your benefit and use.  I hope you find them helpful.  Feel free to let me know what you think and, if you like them, how you might use them in your teaching.

“Bio Web Conferences” http://sophia.smith.edu/~mbarresi/lab/biowebconferences.html

Best regards,

Michael J.F. Barresi

P.S. additional post on stem cell documentaries coming….

(10 votes)

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A fully differentiated cell took a fascinating journey to become its present self.  For every cell, a precursor cell existed that gave rise to it.  And for every precursor cell, a stem cell existed that gave rise to it.  Understanding precursor cells is an important part in understanding stem cell biology.  Today’s image is from a recent paper in Development that discusses how neuron precursor cell divisions affect development of the cerebral cortex.

The cerebral cortex is the outermost layer or brain tissue, and is commonly referred to as “gray matter.”  During development, the different regions and layers of the cerebral cortex are formed from precursor cells.  These intermediate precursor cells (IPCs) arise from radial glial cells (RGCs), which come from neural stem cells. The different layers of the cortex are formed from radial migration of the postmitotic neurons produced by RGCs and IPCs.  The length of time each RGC or IPC cell resides in the cell cycle regulates the distance its daughter neuron can migrate—cells that exit the cell cycle earlier are able to migrate further, while neurons that are born later cannot migrate as far.  Exploring this connection between the cell cycle and formation of cortex layers, Mairet-Coello and colleagues recently published results showing how two different cyclin-dependent kinase inhibitors (CKIs) regulate different stages of precursor proliferation and affects development of the different layers.  Specifically, p57^KIP2 regulates the cell cycle length of RGCs and IPCs, which in turn affects neurogenesis of layers 5 and 6.  p27^KIP1, however, regulates the proliferation of IPCs, in turn affecting neurogenesis exclusively in layers 2-5.  In the images above, p57^KIP2(red) is found in actively dividing precursor cells (PCNA, green) in two different proliferative zones in the developing mouse brain, labeled SV and SVZ.  The SV contains proliferating RGCs and IPCs, while the SVZ mostly contains proliferating IPCs.  Arrows point to p57^KIP2-postitive proliferating cells.

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

Mairet-Coello, G., Tury, A., Van Buskirk, E., Robinson, K., Genestine, M., & DiCicco-Bloom, E. (2012). p57KIP2 regulates radial glia and intermediate precursor cell cycle dynamics and lower layer neurogenesis in developing cerebral cortex Development, 139 (3), 475-487 DOI: 10.1242/dev.067314

(1 votes)

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