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)

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In December we asked people to share how they moved from research to a career away from the lab bench. Since then, we’ve heard from a number of people, and a few stories are still coming in. Here’s the list so far, with current affiliations:

Keep up and blog on – my route to the Node
Eva Amsen – Community manager for the Node and Online Editor for Development

A career in publishing – a developing story
Jane Alfred – Executive Editor for Development

Educational game designer: where biology, games, and technology meet
Nicole Husain – educational game designer at Spongelab Interactive

From the bench to the science centre
Sarah Gibb – Science and Interpretation Officer at Glasgow Science Centre

A career as editor
Vivian Siegel – Director of the Center for Science Communication at Vanderbilt University, and Editor-in-Chief of Disease Models and Mechanisms.

My transition to patent law
Michael Belliveau – Patent Attorney at Clark & Elbing

My journey to scientific editing
Kara Cerveny – scientific editor at Cell

My journey from bench scientist to clinical ethicist
Michael Szego – fellow in clinical and organizational ethics at the University of Toronto Joint Centre for Bioethics

How fate determined my career as a science journalist
Claire Ainsworth – science journalist

Keeping an open mind – a scientist’s quest for positive change
Sobia Hamid – entrepreneur

(2 votes)

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Here are the highlights from the current issue of Development:

Mutant Xist merely muffles X chromosome

In XX female mammals, inactivation of one X chromosome during development equalises the levels of X-linked gene products in females with those in males. Expression of the Xist gene from one of the two X chromosomes produces a non-coding RNA that coats and silences the chromosome from which it is transcribed. But how does Xist RNA induce chromosome silencing? Xist^IVS, an Xist mutant generated in mice by gene targeting, may help to answer this question, suggest Takashi Sado and co-workers (see p. 2649). In embryos carrying the Xist^IVS allele, they report, Xist^IVS is differentially upregulated, and its mutated transcript coats the X chromosome in cis in embryonic and extra-embryonic tissues, but X-inactivation is incomplete. This partial X-inactivation seems to be unstable, and the mutated X chromosome is reactivated in some extra-embryonic tissues and possibly in early epiblastic cells, suggesting that the RNA encoded by Xist^IVS is dysfunctional. Further studies of this unique mutation could thus reveal exactly how Xist RNA induces chromosome silencing.

It’s a wrap: Gpr126 and myelination

In the vertebrate peripheral nervous system, Schwann cells form the myelin sheath, the multilayered membrane that insulates axons and allows the rapid propagation of electrical signals. Now, on p. 2673, William Talbot and colleagues report that, as in zebrafish, the orphan G-protein-coupled receptor Gpr126 is essential for myelination and other aspects of peripheral nerve development in mammals. The researchers show that a mutation in Gpr126 causes a severe congenital hypomyelinating peripheral neuropathy in mice and reduces the expression of differentiated Schwann cell markers. In addition, Gpr126 mutant mice lack Remak bundles (the non-myelinating Schwann cells associated with small calibre axons), and exhibit delayed sorting of large calibre axons by Schwann cells, suggesting that the Schwann cells are arrested at the promyelinating stage. Finally, they report, Gpr126 mutant mice develop abnormalities in the perineurium (the connective tissue that surrounds each nerve fibre bundle). Given these results, the researchers suggest that Gpr126 might represent a target for the treatment of demyelinating diseases of nerves.

Production rates scale the Bicoid gradient

Embryonic patterning is insensitive to embryo size. Consequently, despite size variations among individuals in a population, their body parts are proportionate or ‘scaled’. But how is scaling achieved and do similar mechanisms control within-species and between-species scaling? On p. 2741, Jun Ma and colleagues use embryos from Drosophila melanogaster lines selected for large and small egg volumes to investigate the within-species scaling of the Bicoid (Bcd) morphogen gradient. They show that large embryos contain more maternal bcd mRNA than small embryos and, as a result, have higher anterior nuclear Bcd concentrations. This difference in the anterior production rate of Bcd leads to the scaling properties of the Bcd gradient. That is, in broad regions of large and small embryos, similar Bcd concentrations are found at the same relative embryonic positions. Thus, propose the researchers, unlike between-species scaling, which probably involves species-specific differences in Bcd diffusion and/or decay rates, within-species Bcd gradient scaling depends on the scaling of Bcd production rates with embryo volume.

Plane speaking: the roles of Dachsous and Frizzled

In epithelial tissues, the polarisation of cells within the plane of the tissue helps to coordinate morphogenesis. The Dachsous (Ds) and Frizzled (Fz) signalling systems play key roles in establishing and maintaining this planar polarity but how these systems interact is unclear. Now, on p. 2751, Seth Donoughe and Stephen DiNardo report that the ds and fz genes contribute separately to planar polarity in the Drosophila ventral epidermis. The cuticle of fly larvae is covered with denticles, protrusions that help the larvae move. To investigate how this polarised pattern of denticles is established, the researchers developed a semi-automated method that measures the orientation of individual denticles in the ventral epidermis. Their analyses of various mutants show that ds and fz contribute independently to polarity, that they act over spatially distinct domains, and that the Ds but not the Fz system polarises tissue equally well across small and large field sizes. These and other results provide new insights into the planar polarity machinery.

LMO4: a co-activator of neurogenin 2 in the CNS

Numerous transcription factors regulate the generation and migration of neurons during the development of the central nervous system but the co-factors that support their activity remain unclear. Here (p. 2823), Soo-Kyung Lee and co-workers identify the LIM-only protein LMO4 as a co-activator of the proneural transcription factor neurogenin 2 (NGN2) in the developing mouse cortex. The researchers show that LMO4 and its binding partner nuclear LIM interactor (NLI) form a multi-protein transcription complex with NGN2. This complex, they report, is recruited to the E-box-containing enhancers of NGN2 target genes, which regulate various aspects of cortical development, and activates NGN2-mediated transcription. Consistent with this finding, the researchers demonstrate that neuronal differentiation is impaired in the cortex of Lmo4-null embryos, whereas expression of LMO4 facilitates NGN2-mediated migration and differentiation of neurons in the embryonic cortex. These results suggest that the LMO4:NLI module promotes the acquisition of cortical neuronal identities by forming a complex with NGN2 and subsequently activating NGN2-dependent gene expression.

First blood: in vitro haematopoiesis

The conversion of embryonic stem (ES) cells into haematopoietic precursors in vitro could have important clinical applications, but strategies that achieve this feat usually require the use of feeder cells or serum. Now, Po-Min Chiang and Philip Wong describe a method for converting murine ES cells into endothelial cells and blood precursors at low cell densities in a serum-free defined medium (see p. 2833). The researchers identify a set of cytokines and small molecules that are necessary and sufficient to convert ES cells into definitive haematopoietic precursors within 6 days, and by tracking the fate of single progenitors with time-lapse video microscopy they follow this stepwise differentiation process. The determination of haemogenic fate, they report, occurs as early as day 4 of this differentiation protocol. Moreover, BMP4 plays essential time-sensitive roles in both angiogenesis and haemogenesis. This protocol, the researchers suggest, could thus serve as a framework for future studies of human haematopoiesis and for the development of treatments for haematopoietic disorders.

Plus…

As part of the Evolutionary crossroads in developmental biology series, David McClay introduces the sea urchins and discuss how studies of sea urchins have contributed significantly to our understanding of the developmental mechanisms used to build a deuterstome organism.
See the Primer article on  p. 2639

The recent Keystone Symposium on Evolutionary Developmental Biology presented an opportunity to showcase the latest research findings in this multidisciplinary field and, as reviewed by Haag and Lenski, revealed a growing relevance of this research to both basic and biomedical biology.
See the Meeting Review on p. 2633

(1 votes)

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The annual Embryology course at Woods Hole starts again this week. Best of luck to all participants! We thought it was an appropriate time to launch the third voting round to choose a Development cover from images taken by the students in last year’s course.

Meanwhile, the winning image from the first round – a sea urchin chomping down on a piece of seaweed – will appear on the cover of Development vol. 138 issue 13, which will go live online on June 7 (tomorrow!). The image on the left is a sneak preview of the cover. That issue also contains a primer article about sea urchins as model organism, so the cover was a good fit!

Which of these images will be next to appear on the cover of Development? Please vote in the poll below the images. (Click any image to see a larger version.) You can vote until June 20, 12:00 (noon) GMT

1. Dorsal view of the central nervous system of a Drosophila embryo. Neurons and axons are stained with anti-HRP (red). A distinct subset of neurons express even-skipped (green). Nuclei of the body wall stained with DAPI (blue). This image was taken by Joshua Clanton (Vanderbilt University).

2. Pilidium larvae of the Nermertean, Cerebratulus lacteus. Acetylated tubulin (green), serotonin (red), nuclei (blue, DAPI). This image was taken by Meii Chung (UT Austin).

3. Planaria stained with MF20 (green), phalloidin (red) and DAPI (blue). This image was taken by Valeria Merico (University of Pavia).

4. Drosophila embryo (stage 16) immunostained to detect Tropomyosin (purple) in the developing muscle, the Hox gene Ultrabithorax (green), and Spalt (red). This image was taken by Elise Delagnes and Hannah Rollins (UC Berkeley).

(1 votes)

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Four and a half years ago I was introduced to the field of clinical ethics while nearing the end of my Doctorate in Molecular Genetics at the University of Toronto. After attending a talk given by Kerry Bowman, a clinical ethicist at one of the University teaching hospitals, I approached him with some additional questions. The ensuing discussion led to a productive working relationship. Initially, I helped him perform an ethics analysis of a complicated genomics project. He then invited me to participate in some of his other professional responsibilities, opening a door into a new profession. This foray into clinical ethics had a lasting effect; in short order I decided to retire my pipette and pursue a career in clinical ethics.

At the beginning of my PhD, my intention was to pursue a career as an academic scientist. Like many graduate students I experienced both euphoric moments when critical experiments worked and frustrating periods when experiments were not informative. While I enjoyed the scientific process, I had a nagging feeling that a scientific career was not the perfect fit for me. Accordingly, I tried to keep an open mind and got involved in extracurricular activities. I participated in student governance, got involved in science outreach and taught with a non- governmental organization overseas. I also regularly attended a life science career development seminar series meant to expose graduate students to careers outside of academic science. I first met Kerry when he talked about clinical ethics at one of these seminars.

What immediately captured my imagination was the interesting breadth of activities performed by clinical ethicists. In Canada, most large hospitals either employ their own clinical ethicist(s) or have access to a regional clinical ethics service. Clinical consultations are the bread and butter of most clinical ethics programs and are usually triggered by an ethical tension in the provision of patient-care. A conflict regarding a treatment decision or plan, complicated end-of-life decision making, whether to withdraw life support, consent and capacity issues, and disagreement about discharge planning are all examples of clinical cases that may benefit from clinical ethics support. On the organizational level, many ethicists are also involved in the development of hospital policy since good policies may help mitigate future ethical tensions. Teaching is another important facet of clinical ethics. Education serves to raise awareness about ethical issues and can increase the capacity of healthcare workers and researchers to deal with ethical issues in their practice. Many ethicists also conduct independent research and serve on hospital research ethics boards (the Canadian equivalent of research ethics committees).

After deciding on a career track, I knew I needed more education. To address my knowledge gap, I enrolled in a Bioethics Masters program at the University of Toronto. I was fortunate enough to get a scholarship and worked hard over the two year degree to immerse myself into the field of bioethics. I took a generalist approach and chose a course-based professional masters program, which allowed me to take more courses compared to the thesis-based program that was also offered. I completed the degree and am currently a fellow in clinical and organizational ethics at the University of Toronto Joint Centre for Bioethics. The fellowship program is analogous to an apprenticeship program in ethics. Each fellow rotates through the ethics programs of four partner healthcare institutions over the course of a year (3 months is spent at each site). This unique and wonderful experience has given me practical ethics experience that complements the theoretical knowledge I learned in graduate school.

How has a PhD in molecular genetics prepared me for a career in ethics? Interestingly, several of my patients and non-ethicist colleagues have asked about my background and only about half immediately appreciate why a background in genetics might be useful in ethics. The other half usually can’t get over the fact that most of my training is not in philosophy. I view my background in science to be of great relevance. I am able to understand the science behind many emerging technologies in medicine, which is critically important in order to discuss the ethical implications of new technology and recommendations on how to proceed. My science training also heavily contributed to the development of my analytic, writing and presentation skills, which nicely compliments my bioethics education.

The combination of science and clinical ethics training is still quite unusual and has afforded me some unique opportunities. For example, I have been embedded in a genomics centre at a large research institute to work on ethical issues in parallel with scientific innovation. I have also been invited to speak at several interesting venues on topics involving genetics and ethics. As my fellowship is drawing to an end, I am seeking out clinical ethics positions that will allow me to perform all the clinical activities I described earlier and also use my genetics knowledge in a research ethics capacity. I hope to continue working closely with scientists and work on the ethics of the new research as it is being developed. Although not yet employed as a clinical ethicist, I was recently asked to give a talk about clinical ethics at the same seminar series that first introduced me to the field. I graciously accepted and am looking forward to describing my exciting field to other life science students.

(5 votes)

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Position Available: POST DOCTORAL RESEARCHER

With A/Prof Helena Richardson

Cell Cycle and Development Lab

Peter MacCallum Cancer Centre

Melbourne, Victoria Australia

Project: Apico-basal polarity regulators, Signalling pathways and Tumourigenesis

Available from Sept 2011 – contract initially 1 year with scope for extension

Our lab uses Drosophila as a model of tumour development, and through collaboration to translate this into mammalian systems. We seek a highly motivated, suitably experienced and qualified individual with a PhD (or submitted PhD thesis). Knowledge and experience in Drosophila Cell Biology, Genetics, Molecular Biology and Biochemistry is essential, and expertise in Drosophila imaginal disc biology and tissue culture is desirable. Applicants must have good organisational and communication skills, attention for detail, and the ability to carry out work efficiently and independently.

The Peter MacCallum Cancer Centre is Australia’s foremost Cancer Centre, and has an internationally renowned research division covering Cancer Cell Biology, Genomics and Immunology.

Peter Mac offers its employees the following benefits:

• Salary Packaging
• Employee Assistance Program
• Central City Location
• Supported Education Programs
• Training and Development Program

Please send your CV to email: Helena.Richardson@petermac.org

For further information on my lab see:  http://www.petermac.org/Research/CellCycleDevelopment

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A 2 year post-doc position is available from October 2011 in Delphine DUPREZ’s team, in Paris.

Tendon and ligament injuries are common clinical problems during aging or following accidents. No treatment currently exists to restore injured or defective tendon/ligament to its normal condition. The ultimate aim of this project is to build an in vitro tendon (or ligament) for implantation into patients with defective tendons. The global strategy is to use the knowledge that we have acquired (and that we are currently acquiring) concerning tendon formation during embryonic development using the chick and mouse models (Lejard et al., 2011 J. Biol. Chem 286(7), 5855-5867, Wang et al., 2010 Dev Cell, 18, 643-654, for review Tozer and Duprez, 2005, Birth Defects Res C Embryo Today. 75(3), 226-36) in order to establish an artificial tendon.

The project will involve cell culture of adult mesenchymal stem cells and transfection experiments with the appropriate factors in order to trigger cell differentiation towards a tendon phenotype. The project will also require in vivo manipulations in chick embryos, the use of mouse mutant lines and the use of rat tendon injury models.

A background in mesenchymal stem cells and/or cell culture will be an advantage.

Applicants may be of any nationality and should have obtained the equivalent of a PhD. Salary will be at least 2500 Euros per month (depending upon experience). Applications including a CV, a description of previous research experience, and 2 or 3 names of referees should be sent to Delphine DUPREZ to Delphine.duprez@upmc.fr

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Each year, three medals to honour extraordinary research achievements in cell and developmental biology are awarded at the joint conference of the British Societies for Cell Biology (BSCB) and Developmental Biology (BSDB). Here on the Node, Eva has recently posted an interview with Carlos Carmona-Fontaine, to whom this year’s Beddington medal was awarded, for his PhD work in Roberto Mayor’s lab at UCL in London. Carlos’ talk on collective migration of neural crest cells was highly entertaining; Eva’s interview gives an impression of the entertainment value – I highly recommend having a look!

The BSCB’s Hooke Medal honours a person who has made an outstanding contribution to UK cell biology within the first 10 years of establishing his or her own lab. 2011’s recipient is Alex Gould (NIMR, London, UK). Together with his team, Alex determined the scheduling mechanism that terminates proliferation of neuroblasts in the Drosophila central nervous system at the end of development. Their second big discovery was uncovering the function of Drosophila hepatocyte-like cells, called oenocytes, which regulate fat metabolism in the fly. In his lecture he mainly presented their most recent research on organ sparing during nutrient restriction: Starvation of fly larvae slows tissue growth, except in the brain. Sparing of the brain is a phenomenon that is also known to occur in mammals. The Gould lab carefully characterised brain sparing in starved fly larvae and identified the molecular mechanism responsible for sparing growth of the central nervous system.

Finally, the BSDB’s Waddington Medal is awarded for outstanding research performance as well as services to the developmental biology community. The awardee is announced only at the meeting; this year it was Chris Wylie (Cincinnati Children’s Hospital Medical Center, USA). His first comment when coming on stage was, “I feel like a dinosaur that’s just been dug out!” Yet, far from resembling a fossil, Chris gave a lucid seminar that described the broad sweep of his research career, which has been largely dedicated to understanding primordial germ cells, the embryonic precursors of gametes. Chris highlighted how the direction of his research has been heavily influenced by the arrival of technological advances over the years. Chris himself has made a major contribution to these advances, being the first to use morpholinos to knock down zygotic genes in the early Xenopus embryo. More recently he has developed an interest in post-natal development of vertebrae and presented some exciting new data on growth and differentiation of intervertebral discs after birth, making a strong case for this kind of research to tackle post-natal disorders.

Chris did not miss the opportunity to give some advice to younger scientists. In his opinion, we should be cautious about believing too strongly in any accepted dogma, since he has seen even the most well established models overturned. He also advises collaboration and, if possible, to find the “perfect partner” – a reference to his long-standing scientific collaboration with his wife, Janet Heasman. Finally, Chris believes we should never follow old scientists’ advice as they grew up in a completely different era – in his case an era when supervisors would allow their PhD students to publish single author papers! Instead, Wylie believes one can benefit from observing the careers of successful senior scientists and copying their methods.

Maurange C, Cheng L, & Gould AP (2008). Temporal transcription factors and their targets schedule the end of neural proliferation in Drosophila. Cell, 133 (5), 891-902 PMID: 18510932

Gutierrez E, Wiggins D, Fielding B, & Gould AP (2007). Specialized hepatocyte-like cells regulate Drosophila lipid metabolism. Nature, 445 (7125), 275-80 PMID: 17136098

Heasman J, Kofron M, & Wylie C (2000). Beta-catenin signaling activity dissected in the early Xenopus embryo: a novel antisense approach. Developmental biology, 222 (1), 124-34 PMID: 10885751

(7 votes)

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(This interview originally appeared in Development)

Every two years, the German Society for Developmental Biology (GfE – Gesellschaft für Entwicklungsbiologie) holds a scientific meeting for their members. This year, from 23 to 26 March, their meeting was held in Dresden, jointly with the Japanese Society of Developmental Biologists (JSDB). At this meeting, we sat down with GfE President Elisabeth Knust to learn more about her and about the society’s role in connecting developmental biologists in Germany.

What is your lab working on?

My lab is working on major questions in cell polarity, in particular on the elucidation of the mechanisms that maintain cell polarity, and we are concentrating specifically on polarity in epithelial cells. Some years ago, we identified what is now called the Crumbs complex. We’re now trying to understand how this complex controls cell polarity. For the past few years we have also been working on photoreceptor cells. We know that the Crumbs complex is involved in the function and development of these cells by controlling shape and morphogenesis. Flies that do not have Crumbs in their photoreceptor cells become blind when they’re exposed to constant light, a phenotype reminiscent of a human disease, retinitis pigmentosa 12. Indeed, some of these patients have mutations in one of the homologues of the Crumbs gene, CRB1. Given these different aspects of the function of Crumbs – control of cell polarity, control of cell morphogenesis and prevention of light-dependent degeneration – we are asking what the complex is doing at a cell biological level. I expect that the function is the same but that the readout of each cell is slightly different. However, this is what we have to figure out.

You’re also the current President of the GfE. How long have you been president of the society?

I’ve been president since 2010 and presidency is always a two-year period. The main task of the President is to organise the meeting, which we are currently holding here in Dresden. The society also runs the GfE school, a symposium particularly for young scientists – graduate students, postdocs – to present their work. This school also takes place every other year and is organised by Ulrich Nauber, the treasurer of the society, and one or two additional scientists, who determine the topic.

Is the GfE school just open to members or can anyone attend?

In principle, anyone can attend. For GfE members, at least for member students, participation and accommodation is free. The invited speakers also get free accommodation but they are supposed to pay for their travel themselves. I think that’s a good way to keep this meeting affordable while still getting good scientists to present their work. But a major function of this GfE school is also to provide the opportunity for students and postdocs to present their own work.

How old is the society?

The society was founded in 1975 with the goal of fostering developmental biology in Germany. Initially, it was meant to be the society for all German-speaking countries, including Austria and Switzerland, but the number of members in Austria and Switzerland has gone down with time: currently there are only eleven members from these countries.

When the society was founded in 1975, was that just for West Germany at the time?

Yes, it was only for West Germany, because at that time everything was separated. After the unification of East and West Germany, it was not difficult to merge GfE membership because there was very little developmental biology in the eastern part of Germany. There was one Drosophila group in Halle – the group of Gunter Reuter, whose work on position-effect variegation made major contributions to what is now known as epigenetic regulation of chromatin. Today, only about 12% of the members come from the former east, e.g. from Dresden, Berlin, Halle and Rostock.
(more…)

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Howard Hughes Medical Institute (HHMI) is launching a documentary film initiative to bring high quality science to TV. Benefiting from HHMI’s direct access to scientific resources and researchers, the $60 million project aims to give the public an accurate overview of the scientific process, while highlighting compelling stories.

Recently, HHMI announced that the film initiative will be led by Michael Rosenblad, a documentary producer and former president of National Geographic Television. In the HHMI news article, he shares his vision for the project:

“Good science films capture the passion of discovery,” said Rosenfeld. “At their best, they give viewers a vicarious sense of what it is like to be a scientist and to be on an adventure. Through film we can help people imagine — in a vivid way – what it would be like to make a discovery themselves.”

Having a top film-maker work with a scientific institute should lead to interesting films, and I can’t wait to watch them.

(3 votes)

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