Next time you curse your hair for your bad hair day, consider thanking it instead.  The hair follicle has populations of stem cells that aid in skin regeneration after injury, and a recent Development paper unravels a new role for the transcription factor Lhx2 in this process.

Populations of epithelial stem cells in hair follicles serve to rebuild the hair bulb during the normal hair cycle throughout our lives, but they also can migrate to wounded skin in order to aid in skin regeneration.   This ability is quite handy—when the skin in a hairy area is injured, it heals faster and more efficiently than a wound on skin without hair.  Recently, a research group illuminated the importance of the transcription factor Lhx2 in the repair of injured skin by hair follicle stem cells.  Lhx2 functions in organ development, cell fate determination, and stem cell activity in some organs.  In hair follicles, Lhx2 was previously known to regulate the switch between stem cell maintenance and activity.  In their recent report, Mardaryev and colleagues found that Lhx2+ hair follicle cells co-express several stem cell markers.  Following injury, proliferating cells in the adjacent hair follicle were positive for Lhx2 expression, as seen in the images above.  Lhx2 (magenta) expression increases by days 3 and 5 following injury.  Most of the dividing cells (green) also are Lhx2+.  In addition, cell proliferation following injury was reduced in heterozygous Lhx2 knockout (+/–) mice.   Lhx2 ensures wound re-epithelization through its regulation of Sox9 and Tcf4, while at the same time inhibiting normal hair follicle cycling via Lgr5 regulation.

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

 
Mardaryev, A., Meier, N., Poterlowicz, K., Sharov, A., Sharova, T., Ahmed, M., Rapisarda, V., Lewis, C., Fessing, M., Ruenger, T., Bhawan, J., Werner, S., Paus, R., & Botchkarev, V. (2011). Lhx2 differentially regulates Sox9, Tcf4 and Lgr5 in hair follicle stem cells to promote epidermal regeneration after injury Development, 138 (22), 4843-4852 DOI: 10.1242/dev.070284

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Here are the highlights from the current issue of Development:

Skin-deep dermal niches

Hair follicle formation in the epidermis depends on signals from the underlying dermis and normally only occurs during late embryonic and early neonatal life. However, epidermal activation of β-catenin can induce follicle formation in adult mouse skin. One possible explanation for this observation is that epidermal cues can reprogram adult dermis to a neonatal state. On p. 5189, Fiona Watt and co-workers investigate this possibility by examining dermal fibroblasts from adult and neonatal mice. The researchers show that the gene expression profile of adult dermal fibroblasts isolated from skin in which β-catenin has induced ectopic follicles resembles that of neonatal fibroblasts rather than that of fibroblasts isolated from uninduced adult skin. This dermal reprogramming seems to originate within a specific subpopulation of fibroblasts near the hair follicle junctional zone and results in fibroblast proliferation and extracellular matrix remodelling. Together, these results suggest that the adult dermis is an unexpectedly plastic tissue, and that epidermal stem cells and their dermal niche exist in a state of dynamic interdependence.

Self-duplicating escorts for germ cells

During Drosophila egg development, differentiated germ cells, which are produced by germline stem cells (GSCs), are accompanied by escort cells (ECs) to the centre of the germarium, where the germ cells form egg chambers. It has been proposed that these ECs are generated by a population of escort stem cells, but Ting Xie and co-workers now overturn this idea (p. 5087). The researchers show that ECs undergo slow turnover and that lost cells are replaced by self-duplication rather than by stem cell division. Using fluorescent markers, they show that ECs extend elaborate cellular processes that interact with differentiated germ cells and that these processes are missing when GSC differentiation is blocked. Conversely, disruption of Rho function in ECs, which disrupts the formation of EC processes, leads to the accumulation of ill-differentiated single germ cells and the gradual loss of ECs. These findings reveal a mutual dependence between ECs and differentiated GSC progeny, and suggest that self-maintained ECs form a niche that controls GSC lineage differentiation.

Lens invagination Shrooms along

Epithelial invagination, a common feature of embryogenesis, involves coordinated modulation of individual cell cytoskeletons. For example, during eye development, lens pit invagination, which is accompanied by a columnar-to-conical cell shape change (termed apical constriction, AC), is dependent on the cytoskeletal protein Shroom3. Now, through experiments in chick and mouse embryos and in MDCK cells, Richard Lang and colleagues provide new insights into how Shroom3 drives AC and lens invagination (see p. 5177). The researchers show that the activity of Rock1/2 (serine/threonine kinases that activate non-muscle myosin and that are activated by the Rho family GTPase RhoA) is required for lens invagination and that RhoA activity is required for Shroom3-induced AC. RhoA, when activated and targeted apically, is sufficient to induce AC, they report, and is essential for the apical localisation of Shroom3. Finally, they show that the RhoA guanine nucleotide exchange factor Trio is required for Shroom3-dependent AC. Thus, a Trio-RhoA-Shroom3 pathway is required for AC during lens pit invagination.

Merlin casts a spell over glial cell proliferation

Glial cells perform many essential roles in the nervous system but how are their numbers controlled during development? Here (p. 5201), Venugopala Reddy and Kenneth Irvine report that glial cell proliferation in Drosophila is regulated by Hippo signalling, a conserved signalling pathway that controls organ growth and size. They show that Yorkie, the transcriptional co-activator of Hippo, is necessary for normal glial cell numbers and drives glial cell overproliferation when overexpressed. Yorkie activity in glial cells, they report, is controlled by a Merlin-Hippo signalling pathway; other upstream regulators of Hippo (for example, Fat) play no detectable role in glial cell proliferation. They also show that Yorkie affects glial cell proliferation by promoting the expression of the microRNA gene bantam, which, in turn, promotes Myc expression. Because homologues of Merlin, Yorkie and Myc are implicated in human glioma development, the authors suggest that the regulatory links identified here could represent a conserved pathway for the control of glial cell proliferation.

String-ing out stem cell homeostasis and aging

Stem cells contribute to tissue homeostasis throughout life by producing differentiating daughter cells. Consequently, a decline in stem cell proliferation is thought to be involved in tissue aging. But what regulates the cell cycle in stem cells? On p. 5079, Yukiko Yamashita and colleagues report that String (Stg), a homologue of the cell-cycle regulator Cdc25, controls stem cell maintenance, proliferation and aging in Drosophila testes. The researchers show that Stg is highly expressed in germline stem cells (GSCs) and in cyst stem cells (CySCs), the two stem cell types present in Drosophila testes, and that Stg is required for GSC and CySC maintenance and proliferation. Moreover, Stg expression declines with age in GSCs, and this decline is a major determinant of the age-related decline in GSC and CySC function. Notably, restoration of Stg activity reverses this age-associated phenotype but also leads to late-onset tumours. The researchers propose, therefore, that Stg/Cdc25 is a crucial regulator of stem cell function during tissue homeostasis and aging.

Brainy new role for Pax6

Successful development of the brain requires the tight regulation of sequential symmetric and asymmetric cell division. The molecular machinery that regulates the mode of cell division during mammalian brain development is poorly understood but now Magdalena Götz and colleagues show that the transcription factor Pax6, a known regulator of neurogenesis and proliferation, regulates both the orientation and mode of cell division in the mouse cerebral cortex (p. 5067). Using live imaging, the researchers show that, in the absence of Pax6, there is an increase in non-vertical cellular cleavage planes in the cerebral cortex. This phenotype, they report, seems to be mediated by the Pax6 target Spag5, which is a microtubule-associated protein. Moreover, long-term live imaging in vitro shows that Pax6-deficient progenitors generate daughter cells with asymmetric fates at higher frequencies than wild-type progenitors. From these and other data, the researchers propose that Pax6 plays a cell-autonomous role in the regulation of cortical progenitor cell division that is independent of apicobasal polarity and cell-cell interactions.

Plus…

Chromosome silencing mechanisms in X-chromosome inactivation: unknown unknowns

In this issue, fifty years after Mary Lyon proposed her X-chromosome inactivation (XCI) hypothesis, Neil Brockdorff discusses the molecular mechanisms of chromosome silencing during XCI, focusing on topics in which new findings are challenging the prevailing view. See the Review Article on p. 5057

Fifty years of X-inactivation research

The third X-inactivation meeting ‘Fifty years of X-inactivation research’, which celebrated the fiftieth anniversary of Mary Lyon’s formulation of the X-inactivation hypothesis, was an EMBO workshop held in Oxford, UK, in July 2011. Gendrel and Heard review the results presented at the meeting and highlight some of the exciting progress that has been made in this field. See the Meeting Review on p. 5049

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Dates for your calendar
This is a selection of upcoming dates of interest, but it’s by no means an exhaustive list. We’ll try to do these once in a while, but don’t hesitate to write your own posts to let people know about similar deadlines, or leave a comment below. Also make sure to check the eligibility of all scholarships and grants before applying.

Conference registration opening.
November 8 – Start of abstract submission for the ISSCR meeting (June 13-16, 2012)
December 1 – Start of registration for the ISSCR meeting

Conference registration deadlines.
Keystone announced a few upcoming deadlines for conference abstract submissions, including dates for the following meetings:
November 9 – abstract & scholarship deadline for “The Life of a Stem Cell: From Birth to Death” (March 11-16, 2012)
November 16 – early registration deadline for “Angiogenesis: Advances in Basic Science and Therapeutic Applications” (January 16-21, 2012)
November 17 – early registration deadline for “Epigenomics” joint with “Chromatin Dynamics” (January 17-22, 2012)
November 22 – early registration deadline for “Cardiovascular Development and Regeneration” (January 22-27, 2012)
November 30 – abstract & scholarship deadline for “Non-Coding RNAs” joint with “Eukaryotic Transcription” (March 31 – April 5, 2012)

Grants and fellowships:
November 18 – Application deadline for the NSF Graduate Research Fellowship Program (GRFP)
December 16 – Application deadline for the Wellcome Trust’s New Investigator Award
December 16 – Application deadline for the Wellcome Trust’s Senior Investigator Award

Travel funding:
December 1 – The very last day to apply to The Company of Biologists Direct Travel grants, which fund travel for conference attendance. These grants are being discontinued.

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Assistant Professor
Universidade de São Paulo
Tenured Faculty position in Evo-Devo

The Department of Zoology, Institute of Biosciences, University of São Paulo, Brazil invites applicants for a tenured appointment in Evolutionary Developmental Biology at the level equivalent to that of Assistant Professor (Professor Doutor). Candidates should have a strong research focus on the developmental mechanisms of phenotypic evolution. The candidate will be expected to establish and maintain an extramural-funded research laboratory and will have the opportunity to participate in the Department´s PhD program and both graduate and undergraduate teaching. Candidates should have a PhD recognized by the brazilian authorities or proof of request for such recognition and an adequate post-doctoral degree is highly recommended. For further information, please contact Prof Antonio Marques (marques@ib.usp.br)

Application deadline: December 8th, 2011

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The Department of Biology at Syracuse University (SU) invites applications for a tenure-track Assistant/Associate Professor position to support ongoing interests in epigenetics, chromatin, and small RNA biology at SU. We seek applicants who utilize biochemical, genetic, and/or genomic approaches to address chromatin- and/or small RNA-based mechanisms of epigenetic regulation within a developmental context such as, but not limited to, stem cell biology, cell-signaling, or cellular differentiation.

The successful candidate will occupy space in the Life Sciences Complex, a new research facility designed to support collaborative research. This position is part of the epigenetics research focus at SU. The successful candidate is expected to develop an independent, extramurally funded research program and will be expected to interact effectively with colleagues in Biology as well as with colleagues from other departments at SU, SUNY-Upstate Medical University, and SUNY-College of Environmental Science and Forestry. The successful candidate will also be expected to teach undergraduate and graduate courses and develop new courses as appropriate to his/her expertise and the needs of the Department of Biology.
Competitive salary, start-up funds, and laboratory space will be provided. Candidates must have a PhD in any area of biology relevant to this search and productive postdoctoral research experience.

For full consideration applicants must complete an online application at www.sujobopps.com , (#028464) and attach the following documents. Please send documents as follows:  FILE 1 – a cover letter outlining the candidate’s qualifications, a 2-3 page statement of research experience, interests and philosophy, a curriculum vitae, and contact information for three professional references to provide letters of recommendation.  FILE 2 – recent publication #1.  FILE 3 – recent publication #2.

Review of applications will begin December 5, 2011. For questions, please e-mail Eleanor Maine, Chair of the Search Committee, emmaine@syr.edu.

Syracuse University is an Affirmative Action/Equal Opportunity Employer; qualified women and minority candidates are especially encouraged to apply.

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THE MAMMALIAN GENETICS AND DEVELOPMENT WORKSHOP
A meeting of the Genetics Society

Venue: UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH
Date: November 17th 2011.
Organisers: Nick Greene, Andrew Ward & Andrew Copp

The Mammalian Genetics and Development Workshop is an annual meeting covering any aspects of the genetics and development of mammals. Meetings are based on the submitted abstracts, and usually include diverse topics ranging from early mammalian development (not exclusively human or mouse), imprinting and identification of disease genes to human population genetics and association studies. In recent years, presentations on other model systems (such as chick and zebrafish) have also been included where these relate to general developmental questions or disease models.

The meeting is traditionally a venue for post-docs and PhD students to talk rather than laboratory heads and so is an excellent training ground and a friendly, informal forum.

Registration
A £10 registration fee is payable by all attendees on arrival at the meeting.  This fee entitles registrants to attend all of the scientific sessions, and to receive the abstract booklet plus tea and
coffee refreshments on both days.  Speakers and chairpersons will be provided with lunch, free of charge, on the day of their presentation. Other participants will be expected to make their own arrangements for lunch. There will also be a wine reception on the first day of the meeting.

Abstract Submission
All Workshop presentations will be in lecture format .  If you would like to present a paper at the Workshop at this year’s meeting, please e-mail your abstract to the following address: mgd.workshop@ich.ucl.ac.uk by Friday 4th Nov*, specifying your preference for a 15 or 30 min slot. *Due to the late notice there will be some leeway on this closing date for readers of the Node provided you let us know your abstract is coming!

With the authors’ permission, abstracts will be published in Genetical Research.

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After the interview with Ottoline Leyser was posted last week, a discussion on Twitter focussed on the last part of the interview, about parenting.

That interview question referred to a little booklet Leyser published a few years ago, after winning the Royal Society Rosalind Franklin Award in 2007. The book, called “Mothers in Science: 64 ways to have it all” features interviews with mothers who have managed to maintain a career in science while raising children. (Here is a link to the PDF on the Royal Society website.) In the booklet, all featured scientists have a page with a timeline showing the important events in their career and family life. They’re all unique stories, because every situation is different.

When I wanted to address the ensuing Twitter discussion (which you can read in the Storify embedded below) I thought I could add a poll to ask how other people have managed to combine their career with children, or perhaps to ask how others have failed to do so. But I quickly realised that there is no question I could possibly ask for which the answer can be reduced to a set of multiple choice answers. The possible answers would need to include all combinations of which family members are scientists, what the other partner’s job is, the age difference between parents (e.g. one is a postdoc, one a PI), working hours, who took the main child-rearing responsibilities or whether there is a balance, gender, which country you’re in, competition in the field of research, how close together the kids are, and much, much more.

Even a quick show of hands, just to ask who has children or not, would be meaningless if it didn’t account for gender, age, career stage, country, family situation, and desire to even have children in the first place.

So there is no poll. There is no poll because clearly there isn’t one clear-cut problem, and because there is not just one type of family unit.

What Ottoline Leyser’s book did is showcase a group of women who all managed to combine a family with a career in their own way. It’s an example to show that it can be done, but it’s not a collection of recipes for success. Each case really is different, and this Twitter discussion between @fishscientist and @David_S_Bristol tells a different story. (Text continues after the embedded file.)

So are there solutions? One promising step was made last week in the UK, when the Research Excellence Framework (REF) announced that “UK funding bodies have taken an early decision on the arrangements for taking account of maternity leave in the REF. … researchers may reduce the number of outputs in a submission by one, for each period of maternity leave taken during the REF period.”

That doesn’t help most of you, but it positively affects the career progress of a few mothers, and at least changes their stories.

If you have your own story to add, please leave a comment, as a poll was just too complicated….

(3 votes)

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What was new on the Node this month? Here are a few of the highlights from October:

MacArthur genius grant for Yukiko Yamashita

Sasha Terashima interviewed Yukiko Yamashita, one of this year’s MacArthur Fellows. The MacArthur foundation hands out “genius grants” of half a million dollars to a select group of people in all areas of arts, science, and humanities. There is no application process, and recipients are free to choose what they do with the money. Half a million out of the blue, with no strings attached – how would you react if you got that phone call?

“When Yukiko received the phone call informing her about being selected and asking her asking her not to discuss it with anyone except her spouse until the official announcement, she had a hard time believing that it was not a scam. “I called my husband right after I hung up my phone call with the foundation and [he] seriously warned me that ‘if you get a second phone call asking your bank account and pin number, so that they can transfer the award money, don’t give it to them.’” “

Academic teaching
If you teach plant science courses, make sure to have a look at Teaching Tools in Plant Biology. In the comments, Mary Williams give some additional advice.

Meanwhile, Lucia Prieto Godino travelled to Uganda to coordinate a course on insect neuroscience and Drosophila neurogenetics. The course members are graduate students and Junior Faculty from Uganda, Tanzania, Kenya, Malawi, Nigeria, and Cameroon, and in the course they will learn how to effectively use insects to teach or do research in neuroscience. In a later post, Lucia updated us on the course progress after the first few weeks.

One student in the course explains the experiment on olfactory choice in Drosophila that his group performed the day before.

Meetings, Jobs, and more Interviews:
– The entire Company of Biologists Workshop on Growth, Division and Differentiation is covered in a series of posts from the meeting.
– Several PhD and postdoc positions have been posted on the jobs page.
– Interviews with Development Editors Gordon Keller and Ottoline Leyser were reposted on the Node. The interview with Ottoline Leyser sparked a lively discussion on Twitter – more about that later today!

See the full October archive here.

(1 votes)

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It’s that time of the month again, when we upload the desktop calendar for next month. This time an image that you may remember from April – either from the contest on the Node or from the pub quiz at the BSDB meeting.

It’s a sea biscuit during metamorphosis from larval to adult stage. This image, taken by Bruno Vellutini of the Marine Biology Center of University of São Paulo, was the runner up in the Intersection Image Competition held earlier this year.

Visit the calendar page to select the resolution you need for your screen. The page will be updated at the end of each month with a new image, and all images are chosen from either the intersection image contest or from the images we’ve featured from the Woods Hole Embryology 2010 course.

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We have now finished the first two weeks of the course. Over these two weeks the students have learned about Drosophila as a model organism and how to set-up a Drosophila lab. They have learn about the genetics of Drosophila, which took quite some time, but now I am sure it is almost like their mother tongue. They have also learned basics concepts in neuroscience, such as the nature of neural impulse, and basic concepts on how neurons work to produce adaptive behaviors. During the practicals among other things they have learned  how to do muscle recordings of neuronal activity with inexpensive amplifiers. They have recorded from the legs and wing muscles of grasshoppers (see picture 1)! and observed under the microscope a multitude of different insects, which all together helped them to appreciate in the practice the nature of the neural impulse and the diversity of sensory and motor systems used by insects.

The students also now know how to collect virgins for their fly crosses, and how to dissect brains out of Drosophila larvae, and look at them under the fluorescent microscope.  We have managed to install a webcam on the fluorescent microscope, so that the students can take pictures of the fluorescent preparations that they look under the microscope. The images resulting from this system are actually much better than we expected (see picture 2).

The students have learned about mechanosensory, chemosensory, visual and motor systems during the theoretical lectures, and they have looked at the wild type behaviours of flies and other big insects during the practical sessions (see picture 3).

They have also performed inexpensive cutting-edge neurogenetic experiments on genetically modified larvae. It is being intense but the effort is worthwhile, now they are ready for the lab work of the last week, during which they will need to apply everything they have learned!

(3 votes)

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