The research headed by Roger Gomis at IRB Barcelona, with the collaboration of Joan Massagué, describes that the loss of the suppressor RARRES3 promotes the colonization of breast cancer cells in the lung.

RARRES3 could prove to be a useful marker to identify patients with a greater risk of metastasis, as well as providing a target for the development of a specific treatment for preventive strategies after removal of the primary tumour.

A study published today in EMBO Molecular Medicine reveals that the loss of function of the gene RARRES3 in breast cancer cells promotes metastasis to the lung.

The research, headed by Roger Gomis, ICREA Professor at the Institute for Research in Biomedicine (IRB Barcelona), is the result of a collaboration between two IRB labs and Joan Massagué, at the Memorial Sloan Kettering Cancer Center in New York.

The scientists demonstrate that RARRES3 is suppressed in estrogen receptor-negative (ER-) breast cancer tumours, thus stimulating the later invasion of the cancer cells and conferring them “a greater malignant capacity,” says Gomis, head of the Growth control and cancer metastasis lab at the IRB.

This type of tumour accounts for between 20% and 30% of breast cancer cases, the metastasis of which usually occurs in the lung or other soft tissues. This stage of the disease is generally fatal. The studies have been performed in samples from mice and in cell lines and have been validated in 580 samples from primary breast cancer tumours.

The study describes that RARRES3 loss of function allows the breast tumour cell to develop the adhesion capacity of malignant cells when settling in lung tissue. Furthermore, after losing RARRES3 cells also lose differentiation capacity (specialization in a specific cell type), which facilitates the initiation of metastases in distant tissues.

“The transformation of a normal cell into an invasive tumour cell is not just about acquiring capacities but equally important is the loss of certain genes, such as RARRES3,” explains Roger Gomis.

The researchers have established that the detection of the loss of RARRES3 could provide a marker to identify patients with greater susceptibility to lung metastasis.

In addition, they uphold that, in order to enhance cell differentiation and to prevent stem cell capacity, which confers greater malignancy, some patients may benefit from treatment with retinoic acid to prevent metastasis after the removal of the original tumour.

“Treatments with retinoic acid have already been tested for other conditions. We consider that it would be interesting to develop specific treatments for this breast cancer subtype,” says Gomis.

Mónica Morales, postdoctoral researcher, and Enrique J. Arenas, “la Caixa” PhD student, both in Roger Gomis’ lab during the research, appear as first authors of the study. Xavier Salvatella, ICREA Professor and head of the Molecular Biophysics lab at IRB, contributed to revealing the key structure of RARRES3 that explains its dual role in the cell.

The study was partially supported by the BBVA Foundation, which since 2006 provides funding for metastasis research undertaken at IRB Barcelona, and by the Spanish Association Against Cancer” (acronym in Spanish AECC), the Catalan Government, and the Spanish Ministry of Economy and Competitiveness.

Reference article:
RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation
Mònica Morales, Enrique J. Arenas, Jelena Urosevic, Marc Guiu, Esther Fernández, Evarist Planet, R. Bryn Fenwick, Sonia Fernández-Ruiz, Xavier Salvatella, David Reverter, Arkaitz Carracedo, Joan Massagué, Roger R. Gomis. EMBO Mol Med. (2014). DOI: 10.15252/emmm.201303675

ROGER GOMIS, PhD,

This article was first published on the 27th of May 2014 in the news section of the IRB Barcelona website

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Here are the highlights from the current issue of Development:

Enhanced maturation of induced neurons

The ability to reprogram human fibroblasts to neurons in vitro has opened up unprecedented opportunities in disease modelling and cellular therapeutics. Despite this breakthrough, a major challenge in the field is the limited phenotypic and functional maturation of the induced neurons (iNs). Now, on p.2216, Anna Philpott and colleagues report that cell cycle-dependent phosphorylation of key neural determinant Ascl1 affects neuronal maturation both in vivo during Xenopus development and in vitro during reprogramming of human fibroblasts to iNs. The authors show that Ascl1 can undergo phosphorylation at multiple serine-proline sites, and that this multisite phosphorylation represents a means to limit neurogenesis to appropriate levels during development. Disruption of this mechanism using a phosphomutant form of Ascl1 results in enhanced neuronal production in the early Xenopus embryo. Moreover, substitution of the phosphomutant Ascl1 for wild-type Ascl1 during lineage reprogramming not only increases the efficiency of conversion to iNs in the absence of reprogramming factor NeuroD, but also enhances the morphological and functional maturation of the cells. This exciting study suggests a way forward in addressing the roadblock of functional maturation during direct lineage reprogramming in vitro.

A-stroma-nomical role for Wnt in the ISC niche

The intestinal stem cell (ISC) niche is responsible for coordinating the ongoing maintenance and regeneration of the adult gut. Wnt signalling is crucial for stem cell maintenance in the ISC niche, but the source of Wnts remains unclear. Now, on p.2206 David Virshup and colleagues show that epithelial production of Wnt is dispensable for intestinal homeostasis in the murine gut in vivo, contrary to in vitro observations. The authors use genetic ablation studies to eliminate either Porcn or Wls, two crucial components of Wnt signalling, specifically in intestinal epithelial cells. The resulting mice from these experiments are phenotypically normal, but cannot form intestinal organoids in vitro when epithelial-derived Wnt is abolished. The authors show that the latter phenotype can be rescued by co-culturing the cells with purified intestinal stromal cells that endogenously produce both Wnt and R-spondin 3, suggesting a requirement for stromal-produced Wnt in gut homeostasis. Inhibition of Wnt signalling with the pan-Wnt inhibitor C59 results in impaired proliferation and regeneration following radiation injury in mice where epithelial Wnt is already ablated, confirming the importance of stromal-derived Wnts.

Bone repair: a fishy business

Complete bone regeneration following appendage amputation is remarkably efficient in zebrafish, but does not occur in mammals. Both groups, however, can repair bone fractures to varying extents, but whether a conserved cellular mechanism underpins both bone regeneration and repair in the adult zebrafish remains unclear. It is also unclear whether new tissue can be generated in other bony structures apart from the fin. In this issue (p.2225). Gilbert Weidinger and colleagues develop two new models of zebrafish bone repair in fin and in skull, and use these to investigate the mechanism by which bone is repaired. Their findings reveal that, like complete bone regeneration, bone repair in both models involves dedifferentiation of mature osteoblasts followed by proliferation, migration to the injury site and redifferentiation to form new bone. Using live fluorescent reporter-based imaging the authors are able to observe osteoblast differentiation dynamics, and confirm via lineage tracing that mature osteoblasts do indeed contribute to the formation of new bone following injuries in both the fin and the skull.

New start for embryonic nucleoli

Almost every living cell contains a nucleus and, within that, a nucleolus. It is commonly accepted that the nucleolus of somatic cells arises from the nucleolar precursor body (NPB), a large, compact nucleolus present in the oocyte, but whether this is true remains to be definitively shown. Now, on p.2255 Hirohisa Kyogoku and colleagues reveal that the NPB in the zygote, which is inherited from the oocyte, is not required for embryonic and full-term development in the mouse. Instead, the nucleolus in the developing embryo is formed de novo. Using micromanipulation techniques, the authors show that removal of the NPB from the late-stage zygote did not cause any disruption to normal development: the resulting zygote was able to develop to the blastocyst stage and upon implantation gave rise to phenotypically normal pups. Several cell divisions after NPB removal, the authors observed de novo formation of nucleoli from newly synthesized materials. Taken together, these results indicate that the NPB of late-stage zygotes is dispensable for subsequent embryonic development, and that the nucleoli of developing and somatic cells form from de novo synthesized material.

Plus…

Switching on sex

Christian Larney, Timothy Bailey and Peter Koopman review the transcriptional regulation of the testis-determining gene Sry. The authors present an integrated model for Sry regulation, and explain how this model functions to control sex determination in mammals. See the Review article on p.2195

Transcription factor heterogeneity in stem cells

Maria-Elena Torres-Padilla and Ian Chambers review what is known about transcriptional heterogeneity in pluripotent stem cells, focusing on the underlying causes of heterogeneity and how transcriptional heterogeneity can be to the benefit of the whole stem cell population. See the Review article on p.2173

Imaging beetle embryogenesis

This issue’s featured video shows the non-invasive, long-term imaging of a Tribolium embryo from several angles. Read the paper by Strobl and Stelzer to find out how a combination of light-sheet fluorescence microscopy and a new mounting method allowed such imaging, on p.2331

(1 votes)

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Development: Associate Reviews Editor (Stem Cells)
(Maternity Cover)

Based in Cambridge, UK

We are currently seeking applications for the role of Associate Reviews Editor for the stem cell field at Development – as a full time maternity cover position.

Joining an experienced, expanding and successful team, this is an exciting opportunity to make a significant contribution to one of the major journals in the field of developmental biology. Development publishes primary research articles, reviews and other front section content. Over recent years, the journal has expanded its focus in the stem cell field via the publication of high quality research and review articles, and the role of Associate Reviews Editor is an important part of our strategy in this growing area.

Applicants will hold a PhD, ideally in stem cell biology, although outstanding candidates with experience in other areas of developmental biology will be considered. Post-doctoral and/or previous editorial experience are desirable, although we will provide on-the-job training. The successful candidate will have a broad interest in science, the scientific community and publishing. Excellent interpersonal and literary skills, enthusiasm and commitment are also essential requirements for the position.

Core responsibilities:
• Commissioning, handling peer review and developmental editing of material for the front section of the journal
• Writing press releases, article highlights and material for Development’s community website ‘the Node’
• Representation of the journal at international conferences and within the wider scientific community
• Creative involvement in the journal’s development

The Associate Reviews Editor will work alongside an experienced in-house team, including the Executive Editor and current Reviews Editor, as well as with our international team of academic editors.

This maternity cover position provides an excellent opportunity to gain experience on a highly successful life-science journal, and offers an attractive salary and benefits. The position will be based in our office in Cambridge, and is a temporary role envisaged to last up to 12 months.

The Company of Biologists (www.biologists.com) is a not-for-profit organisation, publishing five journals in the biological sciences: the three established journals Development, Journal of Cell Science and The Journal of Experimental Biology, as well as two newer Open Access journals, Disease Models & Mechanisms and Biology Open. The organisation has an active programme of charitable giving for the further advancement of biological research, including travelling fellowships for junior scientists and contributions to academic societies and conferences.

Applicants should send a CV along with a covering letter that summarises their relevant experience and why they are enthusiastic about this opportunity, and states their salary expectations.

Applications should be sent by email no later than 23 June 2014 to miriam.ganczakowski@biologists.com
Informal queries to Miriam Ganczakowski on +44 (0)1223 426 164

Applicants must be eligible to work in the UK.

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Explaining new scientific concepts can be a daunting task for anyone involved in outreach. We are constantly trying to come up with ways to explain, show and describe theories and ideas step by step. I’ve recently stumbled across a new app (albeit only available on ipad) called Adobe Voice that could help out scientific communication.

Describing scientific research is like telling a story and Adobe Voice is an app made for just that. It combines on screen images of your choice with your own voice over in an elegant yet simple manner to guide the viewer through a thought process. It has many pre-set themes and background songs to choose from to help personalise your video, and I’m yet to find a combination that doesn’t look professional!

In developmental biology, visualisation of our concepts and ideas helps explain them, as description alone doesn’t convey the beauty of what we study everyday. These days, videos of the first hours of an embryo’s life are almost always included in any speaker’s presentation on development so why shouldn’t we extend this visualisation to our outreach? If, like me, you are not always able to visit as many schools as you’d like, creating these videos with adobe voice means you can send a part of yourself into classrooms virtually!

With Adobe Voice I have started what will hopefully be a mini-series resource that schools can pick up on. I’m focusing on the first ideas of genetics for a Key Stage 4 class (starting their GCSE curriculum). My first video took maybe an hour from concept to completion – I spent most of that learning how to draw a monkey – and I intend to make many more already.

With so many beautiful images available from developmental biology research, the field is made for showing off and these videos are a simple way of doing it justice. I’ve included my first video above and a link to my blog below where I’ll be putting up further videos over the coming weeks. If you have any suggestions for other videos I could make or other topics to cover please let me know, all feedback is welcome for this new endeavour into the video world!

www.genesandeverythinginbetween.wordpress.com

NOTE 17/06/2014:

The second video in this mini series I’m creating is now up! I’ve played around with the sound settings a bit and used only images included in the app itself to see how far I could stretch its applications to teaching scientific ideas.

This post is part of a series on science outreach. You can read the introduction to the series here and read other posts in this series here.

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FULLY FUNDED PhD POSITION
Regulation of immune cell migration during development in Drosophila

Seeking highly motivated, intelligent and creative student with lab experience and either a bachelor’s or a master’s degree to join a research group studying cell migration at IST Austria for their PhD.

The developmental cell biology team of Professor Dr. Daria Siekhaus is an ambitious new group at IST Austria working in the field of invasive migration of immune cells using Drosophila melanogaster. We genetically identify mutants that affect cellular barrier penetration in the embryo, and characterize them molecularly, cellularly and by live imaging. To complement our international team (working language is English), we seek applications for a graduate student to work on a project involving a mutant we have identified in a lipid metabolism enzyme that has effects on specific aspects of migration, apparently in penetrating a tissue barrier. We seek to understand how this protein functions during migration. The project would involve further genetic characterization of this mutant, live imaging of its migratory behaviors, and genetic and biochemical investigations of its function. This mutant may have a relationship to a known human disease gene and exploring that would also be part of the project as well as an investigation of its roles in vertebrate immune cell function in collaboration with the Sixt group.

IST Austria is a new dynamic interdisciplinary institute that seeks to bring the American graduate student model to Europe.

Must interview by early July 2014 and start in mid September 2014. Would present and defend a thesis proposal in a qualifying exam by the following December, and graduate within three to four years from that point.

For more information about IST Austria and the Siekhaus group please visit:

http://ist.ac.at and http://ist.ac.at/research/research-groups/siekhaus-group/
To apply:

This funded graduate student position is available to any nationality.  To apply and to ask any questions send an email to Dr. Daria Siekhaus (Daria.siekhaus@ist.ac.at).
Include in application:

-CV and official transcript of Bachelors and Master’s (if applicable) grades

-Personal statement (up to 2 pages) about your scientific experience, interests and career goals

– Names and contact information of three people who can write a letter of recommendation

-Any other relevant information

References:

Siekhaus et al, Nature Cell Biology (2010) http://www.ncbi.nlm.nih.gov/pubmed/20495554

Cho, Keyes, … Krasnow (2002) http://www.ncbi.nlm.nih.gov/pubmed/11955438

(Review) Williams MJ J Immuno (2007) http://www.ncbi.nlm.nih.gov/pubmed/17404248

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Every year we give the Node readers the chance to choose their favourite images from a selection of great pictures taken by the students of the Woods Hole Embryology course. Last year you chose 4 beautiful images that featured in the cover of Development, and now is time to make your choice again!

Below are 4 great images from last year’s course. Vote in the poll at the end of this post to choose the image that you would like to see in the cover of Development! You can see a bigger version by clicking on the images.

Voting will close noon GMT on June 9th.

1. Squid (Loligo pealeii) embryo stained with anti-acetylated tubulin (red), anti-serotonin (green), and DAPI (blue,nuclei). Imaged on a Zeiss LSM 700 confocal. This image was taken by Nathan Kenny (University of Oxford), Kathryn McClelland (Institute for Molecular Bioscience, University of Queensland), and Sophie Miller (University of Cambridge).

2. Annelid (Capitella teleta) larvae (stage 8), stained with Phalloidin (cyan, F-actin), anti-acetylated-tubulin (yellow), anti-FMRFamide (red) and Hoechst (purple, nuclei). Imaged on a Leica SP8 confocal. This image was taken by Poulomi Ray (Clemson University).

3. Live late stage embryo of a squid (Loligo pealeii). Imaged with a Zeiss SV8 and a SPOT Flex camera. This image was taken by Brijesh Kumar (Indian Institute of Technology, Kanpur).

4. Eye of a late stage squid (Loligo pealeii) embryo stained with Phalloidin (green, F-actin), anti-acetylated tubulin (red), and DAPI (blue, nuclei). Imaged on a Zeiss LSM 780 confocal. This image was taken by Ezgi Kunttas (Carnegie Mellon University).

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

News & Research:

– This month was a sad one for science, as two renowned  scientists passed away: Robin Holliday and developmental biologist Julian Lewis.

– The Royal Society announced their new fellows list, including several developmental biologists: Cliff Tabin, Liam Dolan, Mandy Fisher and Martin Johnson. EMBO’s list of new members also included developmental biologists.

– Recent papers in Science and Nature Medicine examined the rejuvenation effect that blood from young mice has on old mice

– Nature reviewed the book ‘Embryos under the microscope‘, an overview of the history and science of embryology by J.Maienschein

– The Wellcome Trust announced that in 2016 the first volunteers will receive blood cultured from stem cells.

– And do you like science and beer? The Pint of Science festival is kicking off this week (19th-21st of May) in several countries around the world. If you are attending and would like to write about it for the Node, get in touch!

Weird & Wonderful:

– Buzzfeed collated some fantastic science tattoos.

– Check out this segmentation cake to honour David Ish-Horowicz

– And on the topic of cakes, how about an evolutionary tree of cakes and biscuits?

Evolutionary tree of cakes and biscuits? RT @JohnRunions pic.twitter.com/ONtK9BiSjx

— the Node (@the_Node) May 1, 2014

Beautiful & Interesting images:

– As the weather warms up, time for strawberry mitosis.

– And this comic reveals what the audience is really thinking when you give a talk:  

What people think about during your conference talk, by @upmicblog pic.twitter.com/Exf36cXtAd — the Node (@the_Node) April 29, 2014

Videos worth watching:

– Enrico Coen talks about about his book ‘Cells to Civilizations’.

– Undergraduate students at a science communication course created this short video that uses the cartoon Pokemon to explain concepts of evolution.

– Here is an excellent video introducing DNA and the genome to a lay audience.

– And finally the MPI-CBG Institute in Dresden made their own video to the sound of the song ‘Happy’ (spot the dancing directors!):

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

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This is the final post from our developmental neurobiology seminar this semester. Two students wrote about our discussion of the importance of neuronal activity during synaptogenesis and their professor combined and edited the pieces. As usual, we focused  on development in the vertebrate retina. Hope you’ve enjoyed our contributions, we’ve enjoyed sharing our new-found understanding.

“Use it or lose it.” One of my mother’s favorite phrases, applicable to any number of situations. Fail to practice piano? Don’t use a toy for a while? Realize you’ve forgotten your high school Spanish? “Use it or lose it.”

The concept of “use it or lose it” can also be applied to synaptogenesis and neural circuit development (although I doubt my mother was thinking of this when she used the phrase). The idea of Hebbian connections – that synapse formation and elimination is dependent on activity – has been primarily supported by studies of the neuromuscular junction ^[1]. In general, input neurons converging on dendrites differ in synaptic activity, resulting in more active inputs outcompeting less active inputs for dendrite connection. Inputs with less active synaptic regions are ultimately eliminated ^[2],[3]. Essentially, the less active neurons don’t “use it” and so they “lose it”, with “it” being an electrochemical connection to a neighboring neuron.

Several years ago, investigations of developing connections in the vertebrate retina suggested that this idea of “use it or lose it” might not be the sole mechanism employed within the developing nervous system. Our class recently read and discussed a paper by Kerschensteiner et al. (2009) ^[4]. This detailed study suggested that, in contrast to the classical model, some neuronal connections are formed and maintained in the inner plexiform layer independently of synaptic activity.

Anatomy and Physiology Background: ON and OFF cells in the Inner Plexiform Layer

When light hits the mammalian eye, it changes the electrical properties of photoreceptors so that their downstream partners, bipolar cells, deliver a message to retinal ganglion cells (RGCs), which in turn relay information about visual cues to the brain (see Figure 1). The middlemen in this process, bipolar cells, can be depolarized when light hits photoreceptors (ON cells) or hyperpolarized when light hits photoreceptors (OFF cells). Bipolar cells communicate with RGCs by forming synapses with RGC dendrites in the inner plexiform layer (IPL). This layer is stratified primarily into two sections, an outer layer and an inner layer, where RGCs synapse with OFF and ON bipolar cells, respectively. There are three main types of RGCs – those that only synapse with ON or OFF bipolar cells (monostratified RGCs), as well as RGCs that synapse with both ON and OFF bipolar cells (bistratified RGCs).

Figure 1: Model of primary cell types and their connection patterns in the mouse retina. First, Photoreceptors (teal rods (R) and yellowish cones, (C)) synapse with horizontal cells (purple) and bipolar cells (RB and CB, green) in the outer plexiform layer (OPL). Next bipolar cells synapse with ganglion cells (G, blue) in the inner plexiform layer (IPL). Amacrine cells (red) also synapse with both ganglion cells and bipolar cells in the IPL. Notice the stratification within the IPL based on the ON/OFF status of the bipolar cells. (Reproduced for educational purposes from Development of cell types and synaptic connections in the retina (http://webvision.med.utah.edu/).

During retinal development, RGCs form stratified dendritic arbors with synaptic connections to either exclusively ON bipolar cells (ON RGCs), exclusively OFF bipolar cells (OFF RGCs), or ON and OFF bipolar cells (ON-OFF RGCs). In the latter, RGC dendrites form synapses with ON and OFF bipolar cells such that ON and OFF inputs reside on separate laminar arborizations (e.g., Figure 1). Typically, ON and OFF bipolar cells form similar numbers of synapses with RGC dendrites, regardless of whether the RGCs are monostratified (ON or OFF) or bistratified (ON-OFF).

Neuronal Activity Determines Synapse Density within ON and OFF Layers of the IPL

To test whether this classical “use it or lose it” model for developing neuronal connections held true in the retina, Kerschensteiner et al. created a new transgenic line of mice that were unable to release glutamate from their ON bipolar cells, which is crucial for signaling to RGCs. The authors made a transgenic mouse that coupled the transcription of TeNT, a bacterial protease that inhibits vesicle fusion (which is necessary for presynaptic signaling), with the promoter for mGluR6, a glutamate receptor expressed in ON bipolar cells but not in OFF bipolar cells. Thus, ON cells could not communicate with the RGCs, while OFF cells could. If the classical model explains the development of connections between bipolar cells and RGCs, one would expect retinas in the transgenic mice to have no or very few RGC – ON cell synapses, and many RGC – OFF cell synapses.

As expected, the resulting mice exhibited normal receptive field properties from OFF-RGC connections and reduced or absent responses from ON-RGC ones. The dendritic branching and stratification patterns as well as overall connectivity appeared identical in transgenic and wild-type mice. Normal RGC development in the presence of significantly reduced ON bipolar cell activity indicates that partner selection and dendritic stratification of post-synaptic RGCs occur regardless of bipolar cell activity. These data provide evidence that RGCs are programmed to synapse to either ON bipolar cells, OFF bipolar cells, or both, regardless of presynaptic glutamate release.

By quantifying the density of individual postsynaptic sites in RGCs adjacent to ON bipolar cells in transgenic mice, the authors found that loss of glutamate release correlated with fewer mature synapses adjacent to ON bipolar cells (~50% fewer synapses in transgenic compared to wild-type retinas, Figure 2B). In addition, as might be predicted from the “use it or lose it” model, the density of synapses in bistratified RGCs connecting with the silenced ON bipolar cells was decreased relative to the density of synapses in the arbors connecting with active OFF bipolar cells (Figure 2C).

Figure 2: Density of bipolar-RGC synapses changes in response to glutamate release. A) Post-synaptic densities (PSD95, red) form at specific sites along RGC dendrites (blue) when closely apposed to biploar cell termini (green). B) Heat maps of glutamatergic post-synaptic densities for OFF and ON arborizations in bistratified RGCs. C-D) Graphical comparison of data in B. Values from non-transgenic retinas in black, transgenic animals in red. D/A is dendritic density, P/A is post-synaptic puncta per arbor area, P/D is post-synaptic puncta per dendritic length. Images are select panels from Figure 2 in Neurotransmission selectively regulates synapse formation in parallel circuits in vivo, Nature August 2009 (Vol 460, pp. 1016-1020). Kerschensteiner, D., Morgan, J., Parker, E., Lewis, R. & Wong, R. Used with permission of Nature Publishing Group.

When Kirchensteiner and coauthors examined the underlying mechanism for this decreased density, the “use it or lose it” model didn’t seem to hold true. Using time-lapse imaging, the authors showed that the silenced ON bipolar cells eliminated synapses at a rate comparable to wild-type but initial synapse formation was dramatically reduced. These data indicate that glutamate release is necessary for synapse formation and that elimination of synapses may not be directly tied to the activity of presynaptic input.

When the authors examined synapses at the ultrastructural level, they found even more evidence that “use it or lose it” isn’t the best analogy for synaptogenesis in the IPL. They show that ribbon synapses, the synaptic vesicle anchoring structures implicated in rapid neuronal transmission, are more numerous in the silent ON bipolar cells than in the active OFF bipolar cells (or in active ON bipolar cells in wild-type retinas). These intriguing electron micrographs raise the possibility that post-synaptic signaling, perhaps in response to glutamate, limits ribbon synapse formation.

With this study, Kerchensteiner et al. helped elucidate the role of glutamate release in forming synapses between bipolar cells and RGCs. Interestingly, glutamate release regulates how many synapses are formed between bipolar cells and RGCs but not how many synapses are eliminated, contrary to the classical “use it or lose it” model of synaptic formation. In a follow-up study, published in 2011 ^[5], some of the same authors investigate this teamwork approach to syanpatogensis in the IPL, providing evidence that differential synaptic maturation of axo-dendritic appositions is shaped by presynaptic activity and occurs in a cell type-specific manner. Whether (and how) post-synaptic cells may influence this process still seems to be an open question.

Although the “use it or lose it” analogy doesn’t completely describe what happens during synapse formation in the IPL, it does provide a framework for thinking about what cells need to connect with each other. In the case of bipolar cells and RGCs, it seems that glutamate needs to be used for efficient and robust synaptogenesis or the cells lose out all together, rarely making functional connections.

——————

[1]Kasthuri, N., & Lichtman, J. (2003). The role of neuronal identity in synaptic competition Nature, 424 (6947), 426-430 DOI: 10.1038/nature01836

[2]Wong, R. O. L. & Lichtman, J. W. in Fundamental Neuroscience 2nd edn (eds Squire, L. R. et al.) Ch. 20, 533–554 (Academic Press, 2002).

[3]MILLER, K. (1996). Synaptic Economics: Competition and Cooperation in Synaptic Plasticity Neuron, 17 (3), 371-374 DOI: 10.1016/S0896-6273(00)80169-5

[4] Kerschensteiner, D., Morgan, J., Parker, E., Lewis, R., & Wong, R. (2009). Neurotransmission selectively regulates synapse formation in parallel circuits in vivo Nature, 460 (7258), 1016-1020 DOI: 10.1038/nature08236

[5] Morgan, J., Soto, F., Wong, R., & Kerschensteiner, D. (2011). Development of Cell Type-Specific Connectivity Patterns of Converging Excitatory Axons in the Retina Neuron, 71 (6), 1014-1021 DOI: 10.1016/j.neuron.2011.08.025

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Cosy Science is an informal pub gathering where scientists talk about their research over a pint of beer (or glass of wine!) with anyone who is interested in listening. It is mostly a monthly event, taking place at The Cittie of Yorke pub in London, and everyone is welcome!

As you may know, The Company of Biologists runs a series of workshops for scientists, and we collaborate with Cosy Science to bring some of the exciting research discussed at the workshops to the general public. Our latest workshop will focus on cell polarity, and one of the participants, Dr Suzanne Eaton (MPI-CBG, Dresden) will be joining Cosy Science next Wednesday (21st of May) to bring developmental biology to the pub! Suzanne will give a short talk about how cells communicate to build tissues, and its implications in regulating size, embryogenesis and cancer. After a short break to refill, the floor will be open for questions and friendly discussion. So if you’re in the area, bring along that friend who always wanted to know what developmental biology is all about, and enjoy an evening of pub science sponsored by The Company of Biologists!

Find out more information at the Cosy Science website

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Department of Molecular Biosciences, The Wenner-Gren Institute

Stockholm University is a leading European university offering a multicultural environment in one of the world’s most dynamic capital cities. With more than 60,000 students and 5,000 staff, the University facilitates individual and societal development by providing top quality education that is tightly linked to its internationally recognized research programs.

The Department of Molecular Biosciences, The Wenner-Gren Institute (MBW) unites 30 independent research groups pursuing fundamental questions in molecular cell biology, infection and immunobiology, and integrative biology. The department carries out experimental research primarily investigating the function of genes and cells in tissues and organisms.

Main responsibilities: We are looking for a highly motivated and focused individual to join Professor Christos Samakovlis’s research group. The successful applicant will utilize state-of-the-art approaches aimed at obtaining a fundamental molecular understanding of epithelial morphogenesis, regeneration and malignant growth in Drosophila. The laboratory utilizes genome-wide, tissue-specific RNAi screens, live-imaging and transcriptional profiling. The successful candidate is expected to participate in the comparative analysis of gene function in insect and vertebrate tissues.

Qualification requirements: The applicant must have received a doctoral degree from university in the field of molecular cell biology, developmental biology or genetics. Applicants must have demonstrated productivity in pursueing research in molecular cell biology or bioinformatics. Experience with the Drosophila model system is an advantage. Excellent English language skills, both written and spoken, are a requisite. Further information about the position can be obtained from Christos Samakovlis, christos.samakovlis@su.se

Application: 
The application deadline is June 13, 2014.

Applications should comprise the following:

1. CV, including full contact information and date of birth
2. Personal statement describing research interests (1-2 paragraphs), research
   experience (1–2 paragraphs) and career goals (1-2 paragraphs)
3. List of 2-3 references, please include name, e-mail address and telephone number Stockholm University is an equal opportunity employer

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