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CoB Workshop (Day 4): Epigenetic Memory

Posted by , on 3 July 2012

Reflecting on all the great talks over the course of four days, this meeting has been one of the most enjoyable I’ve been to – I’m sure it was due to equal parts setting and participants. Having a small number of high caliber participants was amenable to lively follow-up discussions either over food, drink, or a friendly game of croquet – again kudos to the organizers and the Company of Biologists.  After yet another fantastic lunch we all abruptly disband to the four corners of the world, but, as someone once said, no party can last forever. Back to the lab, fresh with either new or more refined questions to test.

I leave you with some summary points that were articulated on the last day by Sir John Gurdon. Food for thought if you will.

What is the significance of epigenetic memory? To establish and stabilize the somatic cell identity?

However eventually all things will exchange because the marks that maintain this epigenetic memory are either dynamic or can be perturbed.

Hence, what determines the exchange or transition of epigenetic marks? And, what is the basis of resistance.

Until next time. Cheers.

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12th International Conference on Limb Development and Regeneration, Mont-Tremblant Canada

Posted by , on 3 July 2012

This year’s limb conference was held on the 3-7 June at the scenic Mont-Tremblant, Quebec in Canada hosted at Le Grand Lodge hotel. During the winter, it is one of North America’s most popular skiing destination, but during the summer periods, it becomes a stunning location with views across the mountains of trees and magnificent lakes (see photo).

The conference began with a welcome dinner followed by the evening keynote lecture chaired by one of the organisers, Jacques Drouin. Cliff Tabin unfortunately could not attend to give the keynote lecture, however Denis Duboule “stepped in” and gave a wonderful and exquisite talk on his group’s current work on chromatin remodelling and regulation of the Hox genes.

After a tasty continental breakfast with freshly made pancakes and waffles, the first session of the next day was on ‘Growth and patterning’ chaired by Laura Lettice. The standout talks from this session were by Rolf Zeller (looking at bovine limb development), Gregg Duester (role of retinoic acid in patterning), Sevan Hopyan (cell rearrangements in limb development) and Brian Harfe (role of SHH in early limb buds) with plenty of interesting questions following each talk. The second session on ‘Limb initiation and identity’ was chaired by Chi-Chung Hui, with great talks by Qiyan Mao (cell motility in the zebrafish limb bud) and Yasuhiko Kawakami (role of islet1 in mice hind limb development). The session was followed by the first poster session with attention-grabbing posters by Kelsy Lewis (3D atlas mapping musculoskeletal morphogenesis in mouse limb) and Mandy Mason (roles of 5’ Hoxd genes and Meis2 in bat wing) that drew in large audiences. The evening concluded with a 4-course meal with the main dish being salmon and peach sauce – who would have thought they go together. The free open bar was also handy, which meant unlimited beers and wine for everyone to enjoy.

The third day began with a session on ‘Patterning’ chaired by Benoit Robert with many distinguished speakers such as Marian Ros (5’ Hox genes regulating digits via Turing-type mechanism), James Sharpe (using computational model of digit patterning via Wolpertian positioning information with a Turing-type mechanism) – it is of a nice coincidence that we also celebrate 100 years of Alan Turing’s birth this year as well – and Elazar Zelzar (modulation of chondro-progenitor cells). After lunch, the session concluded with a roundtable discussion on ‘Thalidomide: 50 years later’ by Robert Seegmiller, Trent Stephens and Neil Vargesson. Also present at this discussion was Mercédes Benegbi, a Thalidomide survivor and from the Thalidomide Victims Association of Canada, who gave a very emotional talk on the background of the disaster that started 50 years ago. Very fittingly, she received the longest and loudest applause at the end and reminded everyone (should they have forgotten) why scientists do the research they do and prevent such events occurring again in the future. The next session was on ‘Genetics, human malformations and regeneration’ chaired by Sevan Hopyan with standout talks by Etienne Vincent (roles of BMPs and Msx1 on axolotl regeneration) and Alison Elliott (presenting two patients with longitudinal limb deficiency). The second poster session then followed with stimulating posters by Jessica Rosin (regulatory elements controlling expression of Shox genes) and Matthew Towers (temporal requirement of Shh in chick wing development) – the session was again accompanied with free alcohol.

The fourth day started with a session on ‘Epigenetics, the genome and development’ chaired by Marie Kmita with exciting talks by H. Scott Stadler (role of HOTCHON in chondrogenesis and patterning), John Cobb (characterisation of limb enhancer downstream of Shox2) and Miguel Torres (HoxA cluster epigenetic regulation underlies cell-autonomous generation of proximodistal patterning). Due to a free-slot in the timetable, it was suggested and agreed there would be a discussion by Miguel Torres and Gregg Duester on the role of retinoic acid in proximodistal patterning chaired by Jacques Drouin. Both speakers gave a short presentation outlining their cases on whether retinoic acid is required for proximodistal patterning which drew plenty of discussion from the audience. This was a ‘hot’ debate with many questions remaining to be answered; however it was fantastic to witness two leading scientists putting forward their data and their arguments. For me, personally, this was the talk that I will remember for a long time and was very privileged to have been of attendance. The last session was chaired by Gen Yamada on ‘Comparative approaches and evolution’ with talks by Marie-Andrée Akimenko (actinodins, a fish-specific gene family lost during fin-to-limb transition) and Nicola Illing (5’ Hoxd genes and Meis2 in the bat wing). After more than three days of fantastic talks, posters, food, debates and discussions, the evening ended with cocktails (or sparkling wine), announcement of prizes for talks and posters, the farewell dinner and a gathering around a bomb-fire on the beach. The next day, we all had to checkout of the hotel and depart to Montréal-Trudeau airport and return to our homes. Many thanks go to the organisers and sponsors for a wonderful conference and I hope to attend the next limb meeting in two years’ time, I believe, in Florida. My personal thanks go towards the travel awards I received to allow me to attend the meeting. This report will also be submitted to the BSCB newsletter.

 

 

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Stem Cell Revolutions: A Review

Posted by , on 2 July 2012

Stem cells are often in the media and are promoted as wonder cells that can solve the problems of most diseases. The stories told throughout this film give the story of stem cells behind the hype and describes the  real state of stem cell research and therapies today as well as what we are aiming for in the future! My first thought after watching Stem Cell Revolutions was: wow, is education supposed to be this entertaining? Although I have been working in the stem cell field for a few years now, I learnt a lot from watching this film so a big personal thank you to the makers of the film- Amy Hardie and Clare Blackburn for producing a documentary that provides such amazing and enthralling insights into the stem cell research field.

Stem Cell Revolutions takes us on a journey that begins with how stem cells were discovered around 50 years ago following  the study of patients in Hiroshima who were suffering from radiation damage. Following research examining the “factory where blood cells are made” , the bone marrow, Canadian scientists Till and McCulloch discovered blood stem cells: the first discovery of stem cells!! The story moves on to the discovery of other adult stem cell populations and the development of therapies for example Howard Green’s work on skin grafts and then onto restoring vision in India using stem cells. This then brings us to possibly the most controversial stem cell category, embryonic stem cells, whose discovery is discussed by Sir Martin Evans, who won the Nobel Prize for medicine in 2007 for his discoveries involving embryonic stem cells.

We then change gears and move on to the fascinating story of  how Professor Shinya Yamanaka’s work in which adult cells e.g. skin cells can be turned into an embryonic stem cell-like state, which as Connie Eaves says “turned our understanding of human development on its head” . The field of iPSC research is a relatively new stem cell field and I think what is great in this section is that we learn that this work had its basis in the cloning work completed in frogs by Sir John Gurdon and the creation of Dolly the Sheep by Sir Ian Wilmut. The ending of the film is led by the interesting question ‘Where Could It Lead?’. I for one am excited by finding out where stem cell research leads us in the next decade. Furthermore, the challenges that the stem cell field faces in terms of restrictions by legislation, ethical issues and current limitations of stem cell technology are all dealt with in a manner that gives the truth behind sensationalism reported in the media.

The stem cell story is told via interviews with many of the key players who work at the cutting edge of stem cell research field from Connie Eaves to Sir Martin Evans and Austin Smith to Shinya Yamanaka, many of whom I have been lucky enough to learn from directly, and whose expertise and inside knowledge provide great strength to this film. Additionally, the documentary really shows of the global nature of stem cell research and how communications across the globe are leading to progression.  However, I believe the real genius in this documentary was the inclusion of acclaimed author Margaret Atwood, who provides a perspective from a non-scientist. I particularly enjoyed the challenging interactions between Margaret Atwood and Professor Austin Smith– director of the Cambridge Stem Cell Institute. Another great highlight is the animations and illustrations along the journey- stem cell biology really comes to life via these means. I have to admit I am not sure of the significance of the dancing man, or why we need to see Austin cycling to/from the institute, though the latter really did make me smile.

Stem Cell Revolutions gives us the current status of stem cell research in a captivating yet easy to digest manner and leads us into what is possible in the future! It is a must see for anyone who wants to learn about stem cell biology. It is amazing to think that many discoveries that lie in wait may be uncovered by a very simple question as posed by Margaret Atwood to describe the origins of both art and science:-“What if?”.

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This Month on the Node – June 2012

Posted by , on 2 July 2012

June marked the start of summer in the Northern Hemisphere, as well as the Node’s second birthday. We celebrated this occasion with… a plethora of conferences, courses, workshops, and job postings! It was our busiest month ever, in terms of site visits as well as in number of posts, so let’s see what everyone has been up to.

Courses
The annual Embryology Course started again this month in Woods Hole, and the first update from this year’s students comes from Andrew Mathewson.

“Time has become an abstract concept for my fellow students and me; it seems like we just got here and yet have known one another for months. We engage in science almost every hour of every day. There is no work – only play. I was imaging immunostained plankton on a new Nikon A1 confocal microscope at 3am Saturday morning. I would have gone all night except I did not want to miss Nipam Patel’s famous butterfly lecture at 9am the same morning. Again, this isn’t work. I want to be doing this – and so does everyone else here.”

Meanwhile, a record number of people voted for a Development cover from some of the images taken by last year’s students. This beautiful image of a ribbon worm pilidium larvae (left) won this round.

Registration is also open for another course at MBL: the Gene Regulatory Networks in Development course, starting in October.

Conferences and workshops
The International Society for Stem Cell Research holds its annual meeting. This year, the meeting was held in Yokohama, and even the Emperor and Empress of Japan were there! For a full recap, see the posts by James and Dongjin, and the collected tweets from the meeting.

Later that month, the Company of Biologists held a workshop on epigenetics in the south of England. The Company of Biologists workshops are invitation-only for speakers, but every workshop reserves a few slots for PhD students, postdocs and new PI’s, who can apply to attend. David, Roopsha and Emmanuelle were three of lucky attendees at this workshop, and they wrote about their experience on the Node. If you would like to attend a future workshop, please have a look at the upcoming workshops and find out how to apply.

At the start of June, the fourth annual Young Embryologist Meeting took place in London, and Sorrel reported on the day.

Research
Paul wrote about a new method to improve the quality of images taken with halogen light microscopes, and the effect this might have on developing nations:


“The pages of the Node itself are testament to the power of fluorescent imaging to inspire and delight. Wakayama’s team are hoping that inexpensive modification of existing halogen microscopes in schools and teaching labs will help bring science to life for the next generation of budding researchers.”

AHope Beyond Hypelso on the Node:
-Lots of new jobs on the jobs page

Hope Beyond Hype – a graphic story about stem cells

-The role of TGFβ in zebrafish heart regeneration.

-Registration open for the International Chick Meeting and the Physics of Living Matter symposium.

 

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The Node in Japan

Posted by , on 30 June 2012

Earlier this month, I attended the annual meeting of the International Society for Stem Cell Research, which was held in Yokohama this year. I won’t go into much detail about the meeting itself, because James and Dongjin wrote some great posts about it for the Node. If you haven’t yet read them, take a look:

Day 1 – Welcome to Yokohama
Day 2 – Translation begins here in Yokohama
Day 3 – The Emperor at ISSCR
Day 4 – A complete picture

The ISSCR always encourages tweeting at their conference, and I tried to livetweet some of the talks, where possible. Although there was wifi in all the hallways and lobbies of the conference centre, and in the rooms of at least one of the hotels, there was (almost) no wifi in the seminar rooms or the exhibit hall, which is where everything happened! That may have been one of the reasons that very few people took part in the Twitter conversation. Because we were in Japan, all of the non-Japanese attendees relied on wifi for their tweeting. I did keep track of everyone’s tweets, and collected many of them in a Storify, which you can find below.

One of the things I found on Twitter was a poll started by Paul Knoepfler. He could not attend ISSCR, but set up a poll to ask participants what they thought of the conference. From the percentage distribution of the answers it seems that only about twenty people have responded, but they overwhelmingly voted that the conference was “so so”. Unfortunately none of the respondents left a response, so it’s not clear what they didn’t like, or whether they had attended the conference before. It’s a big meeting, and takes some getting used to if you’ve only been to smaller events. I personally had the impression that there were more clinical and applied posters than in previous years, but the topics covered in the talks were very broad and included a lot of fundamental research.

Another online aspect of the ISSCR Meeting was the new ISSCR Connect, allowing ISSCR attendees to catch up after the conference and see some of the talks in the concurrent sessions that they missed. They’re offered by a staggered schedule. At the moment, people who attended the conference can log in and view the talks from the first group of concurrent sessions. (No link, because it’s only available to meeting attendees.) ISSCR Connect also has a networking section, and three groups – including the Node – used ISSCR Connect to announce a small get-together.

The Node’s meetup was during the Thursday afternoon coffee break, in the Exhibition Hall. The Hall was open to everyone for coffee and posters, and people interested in meeting other developmental biologists could drop by our little corner. Some people stayed for most of the break, while others came by briefly just to say hello or to grab some freebies. To the left is a picture of our little corner before people arrived. (Once they did, I didn’t have time to take photos!)

It was interesting to note that, even though the conference was in Japan, and there were many Japanese people there, I barely met any of them. A few came by the Node coffee break, but only to take some information from the table. It’s unfortunate, because I would have liked to meet more Japanese researchers!

On this same trip, before the conference started, I had a chance to interview Development‘s newest editor, Haruhiko Koseki. He observed that, in general, Japanese students and postdocs are not as likely to join in with social activities or be as assertive as scientists from other countries, and he believes that that might actually affect their success as scientists! The full interview will appear in Development and on the Node later this year, so keep an eye out for that.

Finally, below is the Storify from the conference. (My favourite part is the exchange about invisible mice between “Yogioner” and “R.J.” on Thursday afternoon.)

(more…)

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MBL course: Gene regulatory networks for Development

Posted by , on 28 June 2012

In October, the MBL in Woods Hole will host the 5th high level short course on developmental gene regulatory networks. Course directors are Eric Davidson and David McClay, with Isabelle Peter as Assistant Director.

From the course directors:

“This high level short course on developmental gene regulatory networks will be offered to graduate students, postdocs, and PI’s who wish to adapt or advance network approaches to their own research. The previous 4 editions of the course elicited extremely positive reviews from participants, and the 2012 Faculty includes some of the best scientists in this field in the world. For a description of the Course, the detailed Course Syllabus, and application materials, see http://hermes.mbl.edu/education/courses/special_topics/gern.html

The deadline for registration is August 6.

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CoB Workshop: Epigenetic Memory Day 3

Posted by , on 27 June 2012

Tuesday, third day of the workshop, brings up more arguments to the epigenetic memory debate. Alyson Ashe from Cambridge UK discussed the establishment and maintenance of silencing through generations in worms. Jonathan Chubb presented his work using Dictyostelium and live imaging to investigate pulses of expression and how it relates to epigenetic memory. Neil Brockdorff and Andy Bannister discussed histone modifications and their involvement in chromatin and transcriptional regulation (X inactivation and cancers respectively). Fantastic chunky chips for lunch and delicious Eton mess gave everyone the energy to carry on discussing the existence of early events in reprogramming (Amanda Fisher), X-inactivation in mouse embryos (Atsuo Ogura) and how cell type specificity is kept through mitosis. The workshop atmosphere resembles a chamber music session : epigenetic players take part in a very special session to write a new concerto. The interpretation of the music, however, can also generate few dissonances.

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CoB workshop: Epigenetic Memory, Day 2

Posted by , on 27 June 2012

The day starts with a sumptuous breakfast, and the promise of some great talks. Carl Wu talks about the assembly of histone variants at yeast centromeres. Edith Heard takes us through a journey of how X-inactivation occurs in mice. The talks by the students and postdocs are all very good as well. Helen Blau, then introduces Heterokaryons as a model to study the mechanisms of reprogramming.We break for lunch. The food at the workshop is top class.

The Wiston house is located in a typical English countryside, very green and expansive. After lunch we go on a long walk.  This is a great way to get people talking to each other, and unsurprisingly lengthy discussions  on Epigenetics carry on throughout the walk. Upon arrival to Wiston house, coffee and ice creams  are waiting for us, while Sir John Gurdon enthusiastically teaches and recruits people to play Croquet.

The afternoon session begins with an inspiring talk by Renato Paro on Hsp90, Polycomb and stalled polymerases in transcriptional regulation. We are then served Pimms and lemonade in the garden (a quintessentially English thing apparently!) after which a historian dressed quite appropriately for this setting, briefs us about the Wiston house and its various owners. This sprawling mansion was built in the sixteenth century and has quite a few stories to its credit.

Anna Philpott  gives us a task, we have to come up with the single biggest question in Epigenetic memory (!).  A lively discussion ensues after dinner, which comprises of defining Epigenetics (surprisingly more difficult than you might think!), and then leads to ideas related to Epigenetic inheritance during cell division, and finally Transgenerational epigenetic inheritance is discussed.  In a nutshell, according to John Gurdon, Renato Paro, Steve Henikoff and the others, “Epigenetic memory is to do with processes beyond the DNA sequence, that may be self-templating and result in the inheritance of transcription through the cell cycle”. This session is a real eye opener for me, I don’t know for sure if what I do qualifies as Epigenetics anymore! Will have to clarify that before the workshop ends….

This workshop is one of the best I have been to so far.  I am having a fantastic time listening to talks by those who have shaped our understanding of Epigenetics, through their seminal ideas. The workshop is in an amazing venue and has been organized to absolute perfection. All the talks have been very stimulating, I can’t wait to go back and tell my lab mates all that I have learnt here. The Company of Biologists, please hold a  workshop on germ cells next, so I can come back again!…

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@ICAR 2012: Introductory Workshop on the Mechanics of Plant Growth

Posted by , on 26 June 2012

Please join us on the first day of ICAR 2012  (Tuesday 2nd July 16.00-17.30) for a series of short topical introductions to the field and discussions. Find out how mechanics could enrich your everyday view of plants, and your research!

The mechanics of plant growth is a historically rich field, which has provided great insight into how plants grow. The field is undergoing a recent resurgence due to the development of new experimental methods, new modeling techniques, and the application of new technologies (e.g. micro- and nano-indentation, Fourier transform infrared spectroscopy, advanced imaging and quantification tools, Finite Element modeling).

This Workshop aims at two vital purposes:

  1. to (re)introduce the idea of growth mechanics to the plant community
  2. to provide a forum for imperative discussions regarding the application of a mechanical lens to the study of plant growth.

With short informative talks from:

Siobhan Braybrook (University of Bern, CH)
Arezki Boudaoud (ENS Lyon, FR)
Alexis Peaucelle (Universite de Paris VII, FR)
Daniel Kierzkowski (University of Bern, CH)     
 
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In Development this week (Vol. 139, Issue 14)

Posted by , on 26 June 2012

Here are the highlights from the current issue of Development:

BRAF signalling sets astrocyte numbers

Astrocytes are the most numerous cell type in the mammalian central nervous system but little is known about the regulation of astrocyte precursor proliferation during development. Using the astrocyte marker Aldh1L1-GFP, David Rowitch and co-workers now begin to fill this gap in our knowledge (see p. 2477). The researchers identify two morphologically distinct types of proliferative astrocyte precursor in the developing mouse spinal cord: radial glia (RG) in the ventricular zone and ‘intermediate astrocyte precursors’ (IAPs) in the mantle region. Astrogenic RG and IAPs proliferate in a progressive ventral-to-dorsal manner between embryonic day 13.5 and postnatal day 3, and signalling via BRAF (a RAF isoform that is expressed in the developing nervous system) is both necessary and sufficient to promote astrocyte proliferation. Notably, temporally regulated changes in signalling and cell-cycle regulatory mechanisms restrict the mitogenic activity of BRAF during spinal cord development, thereby regulating astrocyte numbers. Together, these results provide new insights into the temporal-spatial control of astrocyte precursor proliferation during mammalian spinal cord development.

PCP gives directional Notch signalling a leg up

Spatial regulation of signalling pathways during development is essential. In the Drosophila leg, a stripe of cells in each segment expresses the Notch ligand Serrate (Ser) and activates the Notch pathway, which is required to specify joints, in distal cells only. Now, on p. 2584, Sarah Bray, Máximo Ibo Galindo and co-workers reveal that the planar cell polarity (PCP) proteins Frizzled and Dishevelled control this spatial restriction of Notch activation. The researchers show that these PCP proteins are enriched at the distal side of cells in the developing leg and that elimination of PCP gene function in the cells proximal to the Ser-expressing cells alleviates Notch signalling repression, resulting in ectopic joint formation. Mutants that disrupt a direct interaction between Dishevelled and Notch also reduce the efficacy of repression, whereas increased levels of Rab5, an endocytic regulator, suppress ectopic joint formation. Thus, the researchers conclude, PCP controls directional Notch signalling in the Drosophila leg by regulating the endocytic trafficking of Notch.

PGCs hitchhike during gastrulation

During gastrulation, the cells that give rise to internal tissues and organs move into the interior of the embryo. The gastrulation movements of endodermal and mesodermal precursors are regulated by transcription factors that also control their cell fate. However, primordial germ cells (PGCs), which also internalise during gastrulation, are transcriptionally quiescent in many species, so they must use an alternative gastrulation strategy. On p. 2547, Daisuke Chihara and Jeremy Nance identify this strategy by showing that, in C. elegans, PGCs internalise by ‘hitchhiking’ on endodermal cells. PGC adhesion to endodermal cells, they report, is mediated by HMR-1/E-cadherin, which is post-transcriptionally upregulated in PGCs through a mechanism that involves the 3′ untranslated region of hmr-1. The researchers also show that expression of HMR-1 in PGCs is necessary and sufficient to promote their internalisation, which suggests that HMR-1 does not promote PGC-endoderm adhesion through homotypic interactions. Because embryonic endoderm and PGCs are closely associated in many species, this novel post-transcriptional gastrulation strategy might be widely used to promote PGC internalisation.

Foxp1/4 restrict secretory cell fates

The secretory epithelium protects the lungs from inhaled pathogens and other environmental insults that can lead to debilitating diseases, such as chronic obstructive pulmonary disease, by producing mucus. The epithelium contains several cell types, including secretory Clara cells and goblet cells, but the control of these cell fates during lung development and regeneration is poorly understood. Here (p. 2500), Edward Morrisey and colleagues report that the transcription factors Foxp1 and Foxp4 (Foxp1/4) control epithelial cell fate during both of these processes in mice. Loss of Foxp1/4 in the developing lung ectopically activates the goblet cell fate program, they show. Consistent with this finding, Foxp1/4 repress key factors in the goblet cell differentiation program, including anterior gradient 2 (Agr2), overexpression of which promotes the goblet cell fate in developing airway epithelium. Moreover, Foxp1/4 also restrict secretory and goblet cell differentiation during lung regeneration. Thus, by restricting cell fate choices during development and regeneration, Foxp1/4 generate the proper balance of functional epithelial lineages in the lung.

Limb induction Bmps along

The molecular pathways that control limb bud patterning and outgrowth are well understood but less is known about limb field initiation. The current model for this process proposes that retinoic acid sits at the top of a signalling cascade that induces the apical ectodermal ridge, the signalling centre for limb outgrowth. Bone morphogenetic protein (Bmp) signalling, which is involved in later limb development, plays no part in this model, but Juan Carlos Izpisua Belmonte and colleagues recently noticed that Xenopus tadpoles exposed to the Bmp inhibitor Noggin during tail regeneration sometimes develop extra hindlimbs. Here (p. 2557), the researchers show that temporary inhibition of Bmp signalling by overexpression of noggin or by using a synthetic Bmp inhibitor is sufficient to induce extra pectoral fins in zebrafish as well as extra limbs in Xenopus. Bmp signalling, they report, acts in parallel with retinoic acid signalling, possibly by inhibiting the known limb-inducing gene wnt2ba. Based on these results, the researchers propose an expansion of the existing limb induction model.

Out-Foxed: dopaminergic progenitor specification

During nervous system development, the transcription factors Foxa1 and Foxa2 regulate specification of the floor plate and of midbrain dopaminergic (mDA) neurons. However, whether Foxa1 and Foxa2 act directly or indirectly by regulating the expression of sonic hedgehog (Shh), which has similar roles, is unclear. Using chromatin immunoprecipitation followed by high-throughput sequencing, Siew-Lan Ang and colleagues now identify 9160 Foxa2 binding sites that are associated with 5409 genes in embryonic stem cell-derived mDA neuron progenitors (see p. 2625). Foxa2 directly and positively regulates key determinants of mDA neurons, the researchers report, and negatively inhibits transcription factors expressed in the ventrolateral midbrain. It also negatively regulates multiple components of the Shh signalling pathway and upregulates the expression of floor plate factors involved in controlling axon trajectories. These and other results represent the first comprehensive characterisation of Fox2a targets in mDA neuron progenitors and provide a framework for understanding the gene regulatory networks that control the development of this important progenitor population.

PLUS…

Somitogenesis

A segmented body plan is fundamental to all vertebrate species. Segmentation is initiated very early in the developing embryo during the process of somitogenesis. Here, Dale and colleagues provide an overview of somitogenesis and highlight the key events involved in each stage of segmentation. See the Development at a Glance poster on p. 2453.

Stem cell powwow in Squaw Valley

The Keystone Symposium entitled ‘The Life of a Stem Cell: from Birth to Death’ was held at Squaw Valley, CA, USA in March 2012. The meeting brought together researchers from across the world and showcased the most recent developments in stem cell research. Here, Chambers and Schroeder review the proceedings at this meeting and discuss the major advances in fundamental and applied stem cell biology that emerged. See the Meeting Review on p. 2457

Evolutionary crossroads in developmental biology: hemichordates

Hemichordates are a deuterostome phylum and closely related to chordates. They have thus been used to gain insights into the origins of deuterostome and chordate body plans. Rottinger and Lowe introduce representative hemichordate species with contrasting modes of development and summarize recent findings that are beginning to yield important insights into deuterostome developmental mechanisms. See the Primer on p. 2463

 

 

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Categories: Research