Here is part 3 of my report on the 2011 BSCB-BSDB Spring Conference this April in Canterbury. In the first part, I covered Mark Krasnow’s amazing opening lecture on lung development, and in part two I introduced this year’s awardees of the BSCB and BSDB honorary medals.

Here I’ll highlight some of the talks in which the researchers used mathematical or computational modelling to understand and predict the behaviour of their system – in modelling terms they “explored the model’s parameter space”. Modelling your favourite biological system is very popular these days, which might be one of the reasons why a well-attended lunchtime workshop on the topic took place at the meeting. Its main take-home message was that modelling usually takes a lot longer than one might imagine, and therefore one shouldn’t underestimate the need for stable long-term collaborations or having a modeller or programmer in the lab.

The talks involving modelling spanned an array of topics, an indication of the widespread implications of the discipline. The subjects ranged from Enrico Coen‘s (John Innes Center, Norwich, UK) beautiful analyses of growth rates and the establishment of polarity during Arabidopsis leaf development, through Yogi Jaeger‘s (CRG, Barcelona, Spain) and Thomas Gregor‘s (Princeton University, USA) models of fly embryonic development, to Kees Weijer‘s (University of Dundee, UK) computational models of chemotactic cell migration in Dictostylium development and chick gastrulation. Here I’ll focus on just two of the studies.

Marie-Anne Félix (Institut Jacques Monod, CNRS-Université Paris Diderot, Paris, France) presented her lab’s recent work on the effect of quantitative variation within the intercellular signalling network that underlies C. elegans vulval development. Using a computational model of this network they varied the parameters of the model, without altering the network’s architecture, and analysed the phenotypic outcomes. A large fraction of the solutions turned out to result in the wild type pattern of vulva cell specification. Previously, two competing models of vulva cell precursor induction – one morphogen-like, the other involving a sequence of direct cell-cell signalling events had been proposed. Examining the parameter sets generated by the computational analysis revealed that they corresponded to either one or the other, or a mixture of the two mechanisms. This suggested that the two experimentally proposed mechanisms can function independently or in concert via the same network topology with the relative contribution of the two mechanisms depending on the quantitative tuning of parameters. Finally, Marie-Anne showed that inter-species differences in vulval patterning can be achieved by quantitative modulations of the very same network.

Denis Headon‘s lab (The Roslin Institute, University of Edinburgh, UK) is interested in vertebrate skin field patterning: Regional differences in the skin’s periodic micropattern of hair or feather follicles constitute the skin’s macropattern. To tackle the molecular pathways underlying macropattern generation, they took advantage of the Naked neck mutant, a naturally occurring chick mutant with a bare neck and lower overall feather density. Having pinned down the insertion associated with the trait, they identified increased levels of BMP12/GDF7 as the cause of the naked neck phenotype. They found that neck skin is more sensitive to BMP than the rest of the body since it selectively produces retinoic acid, which amplifies the effect of elevated BMP. This results in the complete loss of neck feathers. To validate the hypothesis, Denis showed the results of a mathematical model of the reaction-diffusion system of inhibitors and activators known to produce the periodic micropattern of feathers. Testing whether varying inhibitor (BMP) sensitivities, might lead to the macropatterning phenomenon observed in the mutant confirmed that a sharp pattern boundary between neck and body could explain the differences in feather density between neck and body, both in the wild type and at different BMP signalling levels. The simulated and experimental patterns astonished me as they looked more like graphic design than biology – it’s definitely worth having a look!

With these talks, the meeting provided examples of how modern developmental biology is indeed alive and kicking. To include modelling in the analysis is clearly one of the effective directions the field is taking, and in my final post on the Canterbury meeting I’ll highlight one of the other fruitful directions – live imaging.

Hoyos E, Kim K, Milloz J, Barkoulas M, Pénigault JB, Munro E, & Félix MA (2011). Quantitative variation in autocrine signaling and pathway crosstalk in the Caenorhabditis vulval network. Current biology : CB, 21 (7), 527-38 PMID: 21458263

Mou C, Pitel F, Gourichon D, Vignoles F, Tzika A, Tato P, Yu L, Burt DW, Bed’hom B, Tixier-Boichard M, Painter KJ, & Headon DJ (2011). Cryptic patterning of avian skin confers a developmental facility for loss of neck feathering. PLoS biology, 9 (3) PMID: 21423653

(5 votes)

Loading...

The 3D spatial arrangement of DNA within the nucleus is tightly controlled and has great functional significance. Each chromosome has been shown to occupy a defined nuclear territory and the expression of genes is often closely linked to where they are located, with similar expression levels seen for genes with similar locations. It has also been shown that disrupting localisation affects gene regulation.

A new paper, in Genes & Development, has investigated the importance of spatial positioning in the inactivated X chromosome. The X chromosome is considerably larger than its alternative, the Y chromosome, as such males often have one copy of a gene (on the X, with no Y equivalent) whilst females have two. This disparity can cause difficulties in correct gene activity and so regulatory mechanisms are needed. In mammals, females prevent a doubling of X activity by shutting down the activity of one, generating an inactive X chromosome.

This research has shown that the gene silencing involved in X inactivation is connected to the spatial arrangement of the chromosome within the nucleus. For the active X, long stretches of DNA from different parts of the chromosome form many stable associations which are consistently maintained in different cells, with different interacting regions corresponding to active and inactive genes. However, Splinter et al. have shown that the inactive X chromosome is randomly packaged with a lack of consistent interactions.

Within the disordered inactive X conformation, the group were able to identify some genes with spatial architecture suggestive of active gene expression, these ‘escapees’ form long-range contacts with each other, similar to those seen for active genes on the active X chromosome, and other regions of the genome. These observations have effectively doubled the number of ‘escapees’ which now require further investigation.

Of the active genes identified, Xist, a non-protein coding RNA, which is known to be involved in X inactivation, is of particular interest. It has now been shown that Xist may function by affecting chromosome topology. Loss of Xist correlated strongly with a switch to the ordered, active X conformation but did not cause gene reactivation or alterations to the histone code.

Study of spatial arrangements within the nucleus has added a whole new dimension to our understanding of gene regulation. The inactive X chromosome is a particularly striking example of gene silencing, but can be a very useful tool in understanding the intricacies of these regulatory mechanisms and their impact on our lives.

Splinter E, de Wit E, Nora EP, Klous P, van de Werken HJ, Zhu Y, Kaaij LJ, van Ijcken W, Gribnau J, Heard E, & de Laat W (2011). The inactive X chromosome adopts a unique three-dimensional conformation that is dependent on Xist RNA. Genes & development PMID: 21690198

(3 votes)

Loading...

Congratulations to Meii Chung of UT Austin, whose image of a Cerebratulus pilidium larva won first place in the latest voting round to choose a cover for Development from images taken by students of the 2010 Woods Hole Embryology course.

Pilidium larva of the Nermertean, Cerebratulus lacteus. Acetylated tubulin (green), serotonin (red), nuclei (blue, DAPI).

The runners-up in this voting round were Joshua Clanton of Vanderbilt University (fly embryo nervous system), Valeria Merico of the University of Pavia (planaria), and Elise Delagnes and Hannah Rollins of UC Berkeley (fly embryo staining showing tropomyosin/Ubx/Spalt).

Thanks to everyone for participating and voting!

The next round of images will be up on July 11, and in the meantime you’ll be able to read posts from students currently taking the Woods Hole Embryology course.

(4 votes)

Loading...

The Cell: An Image Library is honored to be named a finalist in the website Labby Awards. Please help us win this award and vote for us at the site below. Please be patient if the site does not load right away and apologies for cross posting. Please tell your friends to vote for us as well.
http://the-scientist.com/2011/06/15/2011-labby-website-finalists/

(2 votes)

Loading...

The laboratory of Berta Alsina at UPF-Parc de Recerca Biomèdica de Barcelona is seeking a highly motivated student for a PhD in Inner Ear Sensory Development and Regeneration.

This PhD project will address the question on how FGF and Retinoic Acid signals regulate the development and regeneration of sensory cells and how extrinsic signals are integrated at a molecular level. We use the zebrafish as model system to address these questions. You will be combining functional experiments through transgenic fish lines, in vivo imaging of progenitors and studies of regulatory regions by computational and ChIP experiments. The project provides multidisciplinary training using state-of-the-art techniques and you will therefore be well placed for a future career in biomedical sciences.

The Department of Experimental Life Sciences at Universitat Pompeu Fabra (http://www.upf.edu/cexs/) is part a leading biomedical research center with an excellent international projection. The PRBB (www.prbb.org) , located in front of the sea and highly international, will provide you with a young, dynamic and interacting atmosphere to ensure you opportunities to discuss and learn from experts in diverse fields.

Applicants should have a BSc in biomedical science (or equivalent) amd a master degree with strong academic record to apply to competitive PhD fellowships. Applicants should be highly motivated in the field of stem cell, developmental biology and regeneration and be familiar with developmental biology techniques. Basic knowledge of programming or zebrafish manipulation will be strongly encouraged.

The position will be available from september 2011 for three years. Funding is available for the first year.

If interested please send your application (including CV and BSc academic record) by e-mail to:

Berta Alsina, PhD

Laboratory Developmental Biology

Universitat Pompeu Fabra-PRBB

Dr. Aiguader 88, 08003 Barcelona

Phone: 34-93-3160837

berta-alsina@upf.edu

http://www.upf.edu/devbiol/projectes/Alsina_lab.html

(No Ratings Yet)

Loading...

The fifth international EMT (epithelial-to-mesenchymal transition) meeting will be held this year from Oct 10 to Oct 13 in the beautiful city state of Singapore.  The meeting is co-organized by Jean Paul Thiery and Erik Thompson. It will cover recent development in the EMT field, ranging from basic molecular and developmental mechanisms to translational research (cancer, stem cell and clinical applications).

EMT/MET is a fairly common phenomenon in animal development. For those of you working on basic developmental biology, but interested in having a wider perspective of your research that funding agencies love to hear, this meeting will be a great opportunity.

Conference Website: www.emtmeeting.org

Registration: Early Bird Registration closes on 30 June 2011. Regular registration opens from 1 July.

(3 votes)

Loading...

I’m currently in Toronto for the annual meeting of the International Society for Stem Cell Research (ISSCR), and you can expect to find updates about the meeting at various places. Of course we’ll cover it here on the Node itself, but we’re also using Twitter to share and follow news from the meeting.

The ISSCR meeting has a wonderful media policy, where the embargoes end at the start of each talk, so you can write about them as they happen, and the meeting organisers actively encourage blogging and tweeting. There is an official “Twitter hashtag” for the meeting which you can use to follow along with updates from people who are at the meeting. (That even works if you don’t use Twitter yourself, so don’t worry if you’re not an active social media user.)

This is a link to a list of tweets from people writing about the ISSCR meeting:
all recent tweets tagged #ISSCR2011. (Newest ones are on top.)

I will be using both the Node’s and Development‘s Twitter accounts to post updates as appropriate. You can find those here:
the Node on Twitter
Development on Twitter

And finally, for the official word on the meeting, the ISSCR has its own Twitter account.

(2 votes)

Loading...

POSTDOCTORAL POSITIONS are available to study the cellular and molecular mechanisms controlling the development of the lymphatic vasculature and its functional roles in normal and pathological conditions including obesity and cancer using available mouse models. Highly motivated individuals who recently obtained a PhD or MD degree and have a strong background in molecular, cancer and developmental biology are encouraged to apply. Interested individuals should send their curriculum vitae, a brief description of their research interests, and the names of three references to:

• Guillermo Oliver, PhD, Member
• Department of Genetics
• St. Jude Children’s Research Hospital
• 332 N. Lauderdale, Memphis, TN 38105
• E-mail: guillermo.oliver@stjude.org
• http://www.stjude.org/oliver

(No Ratings Yet)

Loading...

The Drosophila ovary is stunningly beautiful, and a playground of wonderful biological questions.  Within the germarium alone, developmental biologists can look at asymmetric division, stem cells and their niches, cell migration, and cell specification.  A recent paper in Development describes a technique allowing the in vitro imaging of a fruit fly ovary, and opens the door for further studies of development and stem cells.

The Drosophila ovary is composed of about 15 ovarioles, which each houses an organ called the germarium that serves as the assembly line for egg production.  In the germarium, two types of stem cells play important roles – germline stem cells and follicle stem cells.  Germline stem cells divide to kick off the egg production process, while follicle stem cells divide to provide several different types of ovarian follicle cells.  A recent paper by Morris and Spradling describes a technique allowing the live imaging of a developing follicle.  After dissecting and imaging an ovariole in culture, Morris and Spradling were able to monitor cell division, orientation, and movement during follicle generation for a prolonged period.  This technique allows biologists to address many unanswered questions about follicle generation and stem cell biology, as both populations of stem cells can be imaged simultaneously and in their own niches.

Images show a cartoon and high-resolution images of a fruit fly germarium, with germline stem cells (GSC) marked in pink and follicle cells in green (FSC are follicle stem cells).  BONUS!!  For a cool movie of a germarium showing cell divisions and dynamic movement, click here.

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

Morris, L., & Spradling, A. (2011). Long-term live imaging provides new insight into stem cell regulation and germline-soma coordination in the Drosophila ovary Development, 138 (11), 2207-2215 DOI: 10.1242/dev.065508

(1 votes)

Loading...

If you take a look at our Facebook and Twitter pages today, you might notice that they look slightly different. Our regular logo is temporarily replaced with a special logo to celebrate our upcoming first birthday. That’s right – it’s been one year already!

Our official birthday is on June 22nd, and if you check the Node that day, we’ll have a small virtual present for all our readers, as well as a quick look back over the past year.

(5 votes)

Loading...