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...

After a heart attack, heart muscle is irreparably damaged, but a paper in Nature now reports that adult mouse hearts have a source of progenitor cells that can form new muscle cells after heart injury.

A few years ago, studies showed that embryonic epicardial progenitor cells contribute to the cardiomyocyte lineage in developing mouse hearts. These cells were marked by the expression of a key embryonic epicardial gene, Wt1, but Wt1 is not expressed in adult tissues.

The group of Paul Riley at UCL now reactivated Wt1 expression in adult mouse hearts by priming them with thymosin β4 (Tβ4) and inducing injury. This pointed to an adult pool of progenitor cells, marked by Wt1, which could form new cardiomyocytes after myocardial infarction. What’s more, this process was upregulated in response to Tβ4. A few years ago, Riley’s group already showed that Tβ4 also induces formation of blood vessels from epicardial progenitors.

In a video interview with The Scientist, Riley summarized his paper, and emphasized how they built upon previous studies in embryonic heart development to find this new source of adult myocardial progenitors.

Repairing hearts from thescientistllc on Vimeo.

“The key point for us has always been moving back to embryonic development and identifying cells that are key to formation of the organ, that would then translate to repair in the adult.” – Paul Riley (from the interview above)

How exactly Tβ4 induces increased Wt1 expression and cardiomyocyte formation isn’t yet known, but could this be a new therapeutic for heart attack patients? Unfortunately, Tβ4 is not the most practical drug. It would need to be administered before a heart attack, so could only be used as a preventive measure for people who already know they’re at risk, and it’s not available as a pill – only as injection. But a big step toward any form of therapy would be to find out how Tβ4 works at a molecular level to differentiate the progenitor cells to cardiomyocytes upon injury, and, as Riley mentions in the video above, that will be the next step in their research.

update: F1000/The Scientist have some more videos from this lab on their blog.

(more…)

(1 votes)

Loading...