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The Node at the EMBO conference on interdisciplinary plant development

Posted by , on 18 September 2014

The Node is on the road again, but this time not very far! We are going to attend the EMBO conference on interdisciplinary plant development, which starts this Sunday (21st September) at the Sainsbury Laboratory here in Cambridge (UK). We are planning on tweeting with the hashtag  #EMBOplantdev, and will try to include some photos of their beautiful building and the botanical gardens around it! If you are attending the meeting, our community manager will be there, and we look forward to meeting you! We are also looking for someone to blog about the meeting, so if you are interested drop us an email!

 

Node plant EMBO

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Mid-career/Senior Group Leader Position in Stem Cell Biology, Institut Pasteur

Posted by , on 17 September 2014

Closing Date: 15 March 2021

The Institut Pasteur (Paris, France) announces an international call for an outstanding mid-career/senior candidate wishing to establish a new research group in the field of “Stem Cells and Development”. The recruitment is part of the Revive Laboratory of Excellence(LabEx – http://www.pasteur.fr/revive) programme on “Stem Cells and Regenerative Biology and Medicine”. Candidates will be integrated into the cutting edge interdisciplinary environment provided by the Department of Developmental & Stem Cell Biology.

The successful candidate will develop a program specializing in the fields of stem cells, genetics, regeneration, translational research or ageing. He/She will be integrated in an internationally renowned Institute combining fundamental and translational research, in an attractive location in central Paris, in close proximity to other major research centres.

Applications will be evaluated on the basis of scientific excellence. A highly attractive package to match the experience of the candidate will be provided.

Candidates should send their formal applications by E-mail to the Director of Scientific Evaluation, Prof. Alain Israël, at the Institut Pasteur g5revive@pasteur.fr.

Application deadline: December 21, 2014

Short-listed candidates will be invited for interview.

Further information on the Institute and on-campus facilities can be found at http://www.pasteur.fr.

Applicants should provide the following (in order) in a single pdf file:

1. A brief introductory letter

2. A Curriculum Vitae, 10 most important publications and a full publication list

3. A description of past and present research activities (up to 2 pages with 1.5 spacing; Times 11 or Arial 10 font size).

4. The proposed research project (up to 4 pages with 1.5 spacing; Times 11 or Arial 10 font size).

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BSMB/BSDB Joint meeting – The Musculoskeletal System: from development to disease

Posted by , on 11 September 2014

BSMB/BSDB Joint meeting – The Musculoskeletal System: from development to disease

1st -3rd September 2014, University of East Anglia

The first joint meeting of the BSMB and BSDB was, in our opinion, a great success. The meeting was held over three days and was packed with brilliant science from areas of musculoskeletal research from the talks, posters and general discussions. The conference was held in the newly built Julian Study Centre at the University of East Anglia, which boasts well-equipped lecture theatres and small meeting rooms, with inviting break out spaces.

The opening keynote speaker, Tom Rando, provided a brilliant start to the conference with a fascinating account of his group’s work into a primed state of quiescent stem cells, which turned out to be one of the highlights of the conference for me (DB), as it’s closely related to my research. This was followed by an exciting afternoon of presentations within the fields of signalling and development. Standout talks from this session included Gabrielle Kardon on the development of the diaphragm, Malcolm Logan on muscle and tendon formation in the limb and Christine Hartmann on bone development. One great feature of the conference was the opportunities offered to PhD students and post-docs to present their work should they be selected from submitted abstracts. I (GFM) had my abstract selected and was able to present my work during this session along with Anne-Gaelle Borycki, Dylan Sweetman, Susanne Dietrich, Clare Thompson and Sue Kimber. The first day ended with an evening poster session and reception.

The atmosphere at the poster session was exciting and stimulating, fuelled by a couple of glasses of free wine and nibbles, conversations around posters were bustling.  This was my (DB) first opportunity to present some of my PhD work in the form of a poster and the sessions allowed for brilliant discussions of my (DB) work with other students working in the field, but also with experienced researchers. It felt great to be able to discuss and get feedback on my work from my peers.

The second day consisted of two sessions, the first focusing on ‘Mechanobiology and Anatomy’. The session started with a fascinating talk from Eli Zelzer, with his group’s novel take on the mechanics of fracture repair. Other great talks included Mario Giorgi on the role of fetal movement in joint morphogenesis and Chrissy Hammond on jaw development in zebrafish. After a quick coffee break, I (GFM) was hugely impressed with talks by Ronen Schweitzer on tendon growth in the mouse limb and Andy Pitsillides on his group’s work on limb growth and joint formation.

The afternoon session was on ‘Human Genetics and Pathology’ with talks by Mike Briggs, Qing-Jun Meng, Madelaine Durbeej, Linda Troeberg and Veronique Lefebvre. The talks offered a great insight into the current research into various dystrophies and we think this was another ‘plus point’ for the meeting as it allowed the combination of developmental biologists and matrix biologists to share ideas with each other, thus initiating stimulating discussions and possible collaborations.

The conference dinner was held at St. Andrews Hall in the centre of Norwich, a grade 1 listed building dating back to the 14th Century. This provided a great venue and atmosphere for more relaxed discussions of the days events. The three-course meal included salmon, pan-fried lamb and lemon tart (plus unlimited wine!).

The final day played host to the final session on ‘Transcriptional and Epigenetic Regulation’ with great talks by Cay Kielty on genotypes of fibrillinopathies and Simon Tew on gene regulation in chondrocytes. The BSMB also awarded the Young Investigator Award to Blandine Poulet and she gave a lovely talk on her work on modelling osteoarthritis. The final keynote speaker, David Glass, in my opinion (GFM) gave the most fascinating and entertaining talk on his group’s work in developing an antibody treatment for patients with muscular atrophies. It was a great talk to end a fantastic conference. The final session of the day concluded with prizes awarded for PhD students and post-docs for best talk and best posters judged by the invited keynote speakers – this was a great incentive for those who presented their posters and a great way to network.

We would like to give our thanks and congratulations to everyone involved in organising the conference (Ulrike Mayer, Andrea Munsterberg, Graham Riley, Ian Clarke and Tonia Vincent. It was a privilege to be involved in the first joint meeting of the BSMB and BSDB, which we thought was a great success between the two societies and their members, and hope that there will be future joint meetings again. We would also like to thank the BSDB/Company of Biologists for providing travel awards for us to attend.

 

Danielle Blackwell (PhD student) and Gi Fay Mok (Post Doc), Münsterberg lab, UEA

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What is your favourite conference venue?

Posted by , on 10 September 2014

 

Last month I was lucky enough to attend the Xenopus meeting, which took place at the Asilomar conference grounds, close to Monterey, California. This meeting was fantastic, combining great science with a great venue. As there is already someone lined up to write about the scientific aspects of the meeting, I thought I would focus here instead on the venue.

Asilomar is one of the best conference venues I have visited so far. The grounds consist of cabin-style buildings (with fireplaces!) in a pleasant wood, which include accommodation, conference room and cafeteria. Just across the road is the beach and the beautiful californian coastline, there is a swimming pool, and we are surrounded by nature: deer and squirrels in the woods, and whales that can be seen from the coast! Though its natural beauty is definitely a winning feature, what I particularly liked about Asilomar conference grounds was its relative isolation. Conferences are as much about the talks as the interesting discussions that take place in between. When a conference takes place in a big city, attendees tend to stay in different hotels and go their own way after the afternoon sessions, in search of restaurants for dinner. This reduces quite significantly the possibility of chance encounters and hence the opportunity to meet new people and discuss science! This was not a problem in Asilomar, as all the attendees stayed at the grounds and ate all their meals there. And as it was not in a famous world city, there was less of a chance that anyone would skip a session to visit a nearby world attraction! The serene and relaxing location, where you could hear the sea in the nearby beach, kept you could focus on the science and on discussions with the other attendees. At the same time, Asilomar is close enough to Monterey, so that those who wanted to see the local sights (such as the famous Aquarium!) could do so in the free afternoon. And particularly important if you live in the UK, there was that beautiful (and reliable!) californian sun.

This is, of course, my personal perspective, and you may prefer a conference that takes place among the excitement of a big city! What do you think makes the perfect conference venue? Have you been to any conference locations that you thought were particularly good? Let me know what you think by leaving a comment below or on twitter using the hashtag #BestMeetingVenue

 

Asilomar combined

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postdoctoral position — neural crest migration

Posted by , on 9 September 2014

Closing Date: 15 March 2021

A postdoctoral position is available in the laboratory of Dr. Shuyi Nie at Georgia Institute of Technology. The lab employs multiple approaches including developmental biology, cell biology, imaging, and biochemistry to study the mechanisms of neural crest cell migration during embryonic development. Potential projects are investigating the regulation of cranial neural crest cell migration by actin cytoskeletal regulators and the roles of transcriptional factors in cardiac neural crest migration, etc.  The lab is well funded with extramural grants and Gatech start-up.

We are looking for highly motivated researchers with training in development biology, molecular biology, or cell biology. Experience in frog or chick embryology, genomics or confocal microscopy are preferred but not required.

For more information, contact Shuyi Nie (shuyi.nie@biology.gatech.edu). Please send a brief statement of scientific/research interests, your curriculum vitae, and a list of 3 references.

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The origin of blood

Posted by , on 4 September 2014

DEV110841 3319..3323

As for the origin of species, the question of the origin of blood during development has unleashed a lot of passion among the scientific community. As a matter of fact, the failure to derive blood stem cells (haematopoietic stem cells, HSCs) from pluripotent stem cells (stem cells that can generate any type of cells) has generated a lot of frustration for many scientists and has emphasized the need to understand how HSCs first arise during development.

Various researchers have shown that, in the mouse embryo, HSCs emerge in the dorsal aorta in a step-wise manner: endothelial cells lining the dorsal aorta first commit to the haematopoietic lineage (they start to express the surface marker CD41), and further transition to haematopoietic stem cell fate with the expression of the surface marker CD45. Each of these transitions is tightly regulated by precise stage-specific molecular mechanisms and these been under intense scientific scrutiny.

In a recent report published in Development, Liakhovitskaia and colleagues show that the transcription factor Runx1 is not necessary for the first haematopoietic commitment to CD41+ stage but is essential for the commitment to the CD45+ HSC stage.

In the picture you can observe the dorsal aorta of a normal mouse embryo at day 10.5 of development. Blue corresponds to the DNA contained in the cell nuclei. The lining of the aorta is composed of endothelial cells marked by CD31 (green) from which some express the first blood commitment marker CD41 (red). These CD31+CD41+ cells are thought to be the immediate ancestors of HSCs.

Interestingly, the authors further observe that similar CD41+ (red) cells are present in the dorsal aorta of embryos from which the protein Runx1 has been deleted, showing that Runx1 deficiency does not prevent the formation of CD41+ cells. However, Runx1 deficient embryos fail to develop CD45+ HSCs, showing that Runx1 deficiency prevents the progression towards HSC lineage.

Altogether, this report provides a better understanding of Runx1 dependent checkpoints during HSCs development. This small step is another forward step towards the understanding the origin of blood and hopefully towards the generation of HSCs from pluripotent stem cells.

 

Picture credit:

Liakhovitskaia, A., Rybtsov, S., Smith, T., Batsivari, A., Rybtsova, N., Rode, C., de Bruijn, M., Buchholz, F., Gordon-Keylock, S., Zhao, S., and Alexander Medvinsky (2014). Runx1 is required for progression of CD41+ embryonic precursors into HSCs but not prior to this. Development 141, 3319-23. doi: 10.1242/dev.110841

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Designing ChIP primers

Posted by , on 4 September 2014

Hello everyone,

Recently I got assigned with the task of designing good primers for ChIP. My supervisor advised me to use the Primer BLAST tool from NCBI together with AmplifiX to get some computer-generated primers and at the same time test some I designed myself. Problem is we were discussing yesterday and eventually we came up with a question: should the primers include the binding sites for the transcription factor we are interested in or there is no problem if they don’t as long as the binding site is sufficiently close to the region amplified by the primers?

In the meantime I already looked for some info online and the idea I got is that it’s not mandatory that the designed primers include the binding site region. However there is not much more info on the subject (at least that I could find…)

So I would like to ask to people that are more familiriazed with this technique: in your opinion what is the best?

Thank you so much in advance!

Cheers! ;)

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Researchers grow ‘seed’ of spinal cord tissue in a dish

Posted by , on 3 September 2014

Neuromesodermal progenitors (green) generated in a culture dish form normal precursors of muscle (pink)
Neuromesodermal progenitors (green) generated in a culture dish form normal precursors of muscle (pink)

Medical Research Council (MRC) scientists have for the first time managed to turn stem cells into the specialised cells that go on to form spinal cord, muscle and bone tissue in the growing embryo. Their discovery could lead to a new way of studying degenerative conditions such as spinal muscular atrophy, which affects the nerve cells in the spinal column, and may pave the way for future treatments for this and other neuromuscular conditions.

During normal embryo development the spinal cord, muscle and skeleton all form from a group of cells called NMPs (neuro-mesodermal progenitors). This process is driven by a series of carefully timed chemical signals, which instruct NMPs to turn into the different cell types in the growing embryo.

 

By carefully studying and then mimicking this process in a petri dish, researchers at the MRC National Institute for Medical Research and the MRC Centre for Regenerative Medicine, at the University of Edinburgh, were able to coax mouse and human embryonic stem cells into becoming NMPs and then spinal cord cells.

Dr James Briscoe, who co-led the research from the MRC National Institute for Medical Research, said: “There have been some great advances in the field of stem cell research in recent years, with scientists being able to grow liver, heart and even some brain tissue in the lab. The spinal cord, however, has remained elusive because the NMP cells have largely been overlooked – even though they were first discovered more than 100 years ago.

“The real breakthrough for us was realising that we had to coax the stem cells into this intermediate ‘stepping stone’ cell type before turning them into spinal cord and muscle cells. We can’t yet produce the tissues themselves, but this a really big step. It’s like being able to make the bricks and raw materials but not yet build the house.”

Researchers have previously been able to grow some types of nerve, muscle and bone cells in the lab by converting them directly from stem cells. But this is the first time the intermediate NMP cell type, which acts like a ‘stepping stone’, has been created from stem cells. The advantage provided by guiding cells through the routes used in normal development is that the resulting cells may bear closer resemblance to those that occur naturally in the body. This may help any future therapy utilising these cells by providing positional cues to allow them to better integrate with the surrounding tissue.

Neuromesodermal progenitors (green) generated in a culture dish form normal precursors of the spinal cord (pink)
Neuromesodermal progenitors (green) generated in a culture dish form normal precursors of the spinal cord (pink)

In the near-term being able to grow NMP cells in the lab will allow researchers to learn more about normal human development in a part of the embryo that is otherwise difficult to study. In future the method could also be refined to allow scientists to grow tissue from patients with diseases that affect the spinal cord, muscles, or the motor neurones that connect muscles to the brain and spinal cord. This would provide a powerful new tool to study in a dish how these diseases progress and take hold in the body.

Prof Val Wilson, the co-leader of the research from the MRC Centre for Regenerative Medicine, at the University of Edinburgh, added: “NMPs are important because they’re the source of the spinal cord and most of the bones and muscles in our body. But they have been like Cinderella cells. Although recognised for more than a century in the embryo, they’ve tended to be ignored by scientists trying to make these cell types in a dish. We hope this work will bring them out of obscurity and highlight their importance.”

Dr Rob Buckle, Head of Regenerative Medicine at the MRC, said: “This study is a fantastic example of how combining different branches of science can lead to new discoveries. While there have been many important advances in reprogramming stem cells, it’s important that we explore all the possible routes to generating the specific cell types best suited to clinical development. Incorporating detailed knowledge of early developmental processes is likely to play an important role in providing the fine tuning required to achieve this.”

This article was first published on the 26th of August 2014 in the news section of the MRC website.

The paper, entitled ‘In vitro generation of neuromesodermal progenitors reveals distinct roles for Wnt signalling in the specification of spinal cord and paraxial mesoderm identity’, by Gouti et al, is published in the journal PLOS Biology. Further information available from the MRC press office: press.office@headoffice.mrc.ac.uk

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Ethical development

Posted by , on 2 September 2014

This editorial was first published in Development. We encourage feedback from the community on our policies – please leave any comments below.

 

A central premise of scientific publishing – that publication in a peer-reviewed journal means that the reader can be confident that an article is solid – has been challenged on a number of fronts in recent times. In October 2013, John Bohannon managed to get completely fictitious and nonsensical papers accepted for publication in over 100 Open Access journals that supposedly operated a peer-review system(Bohannon, 2013).Around the same time, an article in The Economist (http://www.economist.com/news/briefing/21588057-scientists-think-science-self-correcting-alarming-degree-it-not-trouble) suggested that biotech companies no longer trust the results of published studies from academia, finding them more often than not to be irreproducible (see also Begley and Ellis, 2012). And our own field has recently seen a number of high-profile retractions that have generated significant discussion about research oversight and the reliability of the publishing system for detecting research misconduct, as well as how such cases are handled by institutes, and the mainstream and social media.

Here at Development, and The Company of Biologists more broadly, we take our responsibilities to protect the integrity of the scientific record very seriously. We are members of the Committee on Publication Ethics (COPE) and follow their guidelines and policies in ethical matters (see www.publicationethics.org, for details). Like many other journals, we have a number of checks in place to try and detect potential ethical problems at the earliest possible stage – before publication. Unfortunately, no process is perfect (though we always aim to learn from any mistakes), and there are cases where published papers need to be investigated – and potentially corrected or retracted. Here again, we have clear procedures to ensure this is carried out as carefully, thoroughly and efficiently as possible (while maintaining confidentiality as appropriate), and we are constantly seeking to improve these procedures as policies change and new tools become available. Most of the ethical issues we encounter can be divided into three main categories: authorship disputes, plagiarism and inappropriate data manipulation.

Questions of authorship – who qualifies as an author, and in what order – are ideally agreed between authors well before submission, and adjusted if need be during the revision process. However, different individuals have different ideas as to what justifies authorship on a paper, and the increasingly collaborative nature of science means that assigning authorship is not always straightforward. Development’s guidelines state: ‘An author is someone who has made significant and substantial contributions to a study. This should include conception, design, execution and interpretation of the findings being published, and drafting and revising the article.’ Obviously, not all authors will necessarily have been involved with all stages of the work: consider the student who arrived halfway through a project – and so played no part in ‘conception’, or the lab head who didn’t actually carry out any of the bench work – the ‘execution’. We believe that a detailed ‘Author Contributions’ statement (required in all papers since 2013) is the best way of making it clear who did what on a paper, and in most cases, this works well. We also ensure that all listed authors are kept informed of the progress of a manuscript through our system, so that they can inform us of any potential concerns they may have.

But what about individuals, not listed on the paper, who believe they qualify for authorship? Such cases may only come to light after an article has been published, when the sometimes angry non-author emails us to assert their right to authorship. We aren’t in a position to weigh up the relative contributions of different individuals, so if the relevant parties can’t agree between themselves, we have to refer the case to the relevant institute(s) for them to investigate. This can be lengthy and painful, and serious authorship disputes can even result in papers being retracted from the literature. Our advice? Discuss authorship at an early stage in the project, be prepared to be flexible if contributions change (e.g. during revision, where someone new may have to step in to complete experiments – particularly if original authors have left the lab), keep lines of communication with collaborators and former colleagues open, and ensure that those who don’t quite qualify for authorship are recognised in the Acknowledgements section.

Fortunately, we have not experienced many problems with plagiarism in Development, although it is something we take seriously and police actively. All papers accepted for publication in the journal are run through a plagiarism detection program, iThenticate, that checks for significant matches to other papers or online material. We apply common sense here: there are only so many ways to describe a particular protocol, and original phrasing can be difficult particularly if English is not your native language. What we are looking for are cases where authors have clearly copied from another source without reference, and the degree of plagiarism defines our subsequent action: asking the authors to quote the original article, to rephrase their text, or – in extreme cases (which fortunately we have not yet encountered) – withdrawing the paper from publication. Of course, no software can detect so-called intellectual plagiarism, the ‘stealing’ of ideas, and here we rely on our reviewers and readers to alert us to potential problems, which we can then investigate.

By far the majority of ethical concerns we encounter involve data presentation and manipulation. The Journal of Cell Biology pioneered efforts to educate authors on appropriate figure processing (Rossner and Yamada, 2004) and to screen papers for possible problems before publication, and many publishers, including The Company of Biologists, now employ routine screening procedures to look for potentially inappropriate image manipulation in all accepted manuscripts (our policies on figure preparation can be found at http://dev.biologists.org/site/submissions/figure_prep.xhtml#manipulation). Referees can also play an important part here, by looking at figures with a critical eye when reviewing a paper and by alerting the editor to any potential concerns with data. Of course, it should be noted that an author who really wants to ‘cheat the system’ may be able to do so by clever use of Photoshop, or by manipulating the experiments conducted rather than the data collected. Moreover, our checks are not perfect, although we are always striving to improve them. However, when we do detect inconsistencies of concern – most frequently, unmarked splicing of gel lanes or alterations to the background of an image – we contact the authors, asking them to explain how the data were processed and to send us the original data behind the figure. In the vast majority of cases, authors are able to provide these easily and can reassure us that experiments have been conducted and reported appropriately, alterations can be made to the figure(s) where necessary, and there is no significant delay to publication. More substantial errors, such as duplicating data between panels or figures, can also be detected in some cases; it should be noted that these may be the result of honest error on the part of the author (the careless pasting in of the wrong image when preparing a complex panel) and can also be resolved rapidly. Unfortunately, however, not all instances of data manipulation are ‘innocent’, and we will not publish a paper where questions are hanging over the integrity of the data.

These are the cases that the reader never sees: those that are identified and resolved before publication. The more high-profile cases are those picked up after the paper has been published. Journals are receiving an increasing number of anonymous emails, often relating to papers published many years ago. These can be somewhat obtuse; a frequent complaint is that ‘error bars look too small or too similar to be real’. As responsible publishers, it is our duty to investigate all such complaints, and some real and important cases of image manipulation have been unearthed from anonymous tip-offs. We also receive reports from non-anonymous readers, as well as from the authors of the papers themselves – who may discover problems with their data as they follow it up in subsequent studies. The categories of errors and their frequencies are similar to those we identify pre-publication, as are our steps to investigate them. The first step is always to contact the corresponding author for an explanation; most issues can be readily resolved by an explanation from the authors and the provision of original data – potentially resulting in the publication of a Correction – but occasionally we do find more serious problems that may indicate intent to deceive and that require in-depth investigation.

So what do we do when we do identify serious problems – either before or after publication? As with authorship disputes, it is often impossible for us to resolve questions of data integrity at a distance. In these cases, we ask the appropriate bodies at the authors’ institute(s) to step in. They can look at the history of the research in detail, including going through lab notebooks, freezers and so on. This can take considerable time, although we will endeavour to keep our readers informed where appropriate: we are introducing a policy of publishing a Publisher’s Note to make readers aware of potential problems while investigations are ongoing. In all cases, we will take the necessary action once an investigation is complete to ensure the integrity of the scientific record. This might mean publishing a correction or a retraction.We are fortunate that retractions are rare here at Development, but this does not mean that we are reluctant to retract a paper where appropriate.

One important point to consider is the degree to which publishing policies have changed in the past decade or so. Those ‘manipulations’ that we now deem inappropriate (such as unmarked splicing of gel lanes) were common practice 10 years ago, and it can be unfair to judge the integrity of a paper published several years back by today’s standards. Moreover, manipulated data does not always imply fraudulent activity – authors frequently process their data for clarity or aesthetics without realising that this may not comply with journal policy. Still, many problems can be avoided through good recordkeeping and well-organised long-term storage of the original data (like many institutes, we expect that authors should retain records for a period of around 10 years), and through conservative post-processing of data – so that the submitted image accurately reflects the data gathered.

Simple mistakes can have significant consequences on the conclusions of a line of research. The vast majority of scientists are honest, and should be treated as such unless there is clear evidence to the contrary. Even in cases of clear misconduct, individuals should not be vilified – as an organisation, we take an educational rather than a punitive approach, and it is always important to retain perspective in these cases. It is often argued that the pressure to publish can lead researchers to cut corners, produce sloppy data or even commit fraud. This is no excuse, but in a culture where the rewards for a high-profile publication are so high, it is perhaps inevitable that a small number of people will succumb to these temptations. Fortunately, this is very rare and, at Development, we are proud to have the reputation of publishing papers that ‘stand the test of time’; for this, we are grateful to our editors, reviewers, authors and readers, whose careful work protects the integrity of our papers. Although there is always room for improvement, we hope that the policies we have in place, and continue to review and develop, will help to ensure that we correct any honest mistakes made and remain vigilant to the rare cases of intentional fraud.

 

Olivier Pourquié, Katherine Brown and Claire Moulton

References

Begley, C. G. and Ellis, L. M. (2012). Drug development: raise standards for preclinical cancer research. Nature 483, 531-533.

Bohannon, J. (2013). Who’s afraid of peer review? Science 342, 60-65.

Rossner, M. and Yamada, K. M. (2004). What’s in a picture? The temptation of image manipulation. J. Cell Biol. 166, 11-15.

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In Development this week (Vol. 141, Issue 18)

Posted by , on 2 September 2014

Here are the highlights from the current issue of Development:

 

Mcc: a new player in gastrulation

FigureThe mutated in molorectal cancer (Mcc) gene has been described as a tumour suppressor, and has been shown to interact with β-catenin and thus limit Wnt signalling. However, various data also indicate a potential role in regulating the cytoskeleton. Ray Dunn and colleagues set out to investigate this further in zebrafish and Xenopus (p. 3505). In both species, they find that morpholino-induced mcc knockdown leads to phenotypes typical of defects in convergence and extension during gastrulation. Importantly, these phenotypes can be fully rescued by co-injection withMcc RNA. In zebrafish, the defects in cellular behaviour are very similar to those seen upon disruption of non-canonical Wnt pathway. Through epistasis and biochemical analysis, the authors provide evidence that Mcc is likely involved in transmitting the Wnt signal from Vangl2 to the downstream effectors RhoA and JNK. Although the detailed molecular mechanism remains unclear, these data identify an important role for Mcc as a component of the non-canonical Wnt pathway that coordinates anamniote gastrulation.

Chromatin dynamics in sperm

During spermatogenesis, the chromatin undergoes significant changes in architecture, with histones being largely replaced by protamines, inducing genome-wide condensation. Two papers provide insights into the regulators and mechanisms of this histone-to-protamine transition and its importance for male fertility.

FigureOn p. 3495, Leonard Guarente and colleagues analyse the consequences of SirT1 deletion in pre-meiotic spermatids. SirT1 is an NAD+-dependent deacetylase, the whole body deletion of which has been shown to impair male and female fertility via a systematic effect on reproductive hormone levels. However, whether it is also required in the germ cells themselves is not known. In this article, the authors show that SirT1 depletion specifically in the testis leads to a cell-autonomous defect in sperm maturation and male fertility. They find that histone hyperacetylation – one of the first steps in the chromatin changes of the histone-to-protamine transition – is significantly impaired, with consequent defects in the recruitment of downstream proteins required for histone removal and protamine deposition. Moreover, their data suggest that loss of SirT1 may accelerate reproductive ageing. Although the molecular mechanisms by which SirT1 regulates histone acetylation remain unclear, these data uncover an important role for this protein in the male germline.
FigureMeanwhile, Paul Knoepfler and co-workers investigate the role of the histone H3 variant H3.3 in regulating spermatogenesis (p. 3483). H3.3 is generally associated with active transcription. Here, the authors generate a knockout of one of the two genes encoding H3.3, H3f3b, which leads to a strong reduction in H3.3 levels in the male germline. The mutant mice display a severe defect in sperm morphology and production, and hence in male fertility. Analysis of the chromatin state of H3f3b knockout germ cells reveals an increase in the levels of the repressive mark H3K9me3, and a decrease in H3K4 methylation, a mark of active chromatin. Importantly, the authors uncover defects in the histone-to-protamine transition, with both protamine levels and incorporation being reduced. These data provide the first insights into the role of H3.3 in mammalian spermatogenesis, and indicate an important role for this histone variant in regulating the striking changes in chromatin structure that accompany sperm formation.

 

Root nodule fate map revealed

FigureWhile most plants derive nitrogen (N) from the soil, some plants, such as legumes, can create their own supply by forming specialized root nodules that house N2-fixing bacteria. Nodule tissue ultimately derives from root cells that are reprogrammed to a nodule cell fate during nodule initiation, but exactly which root cells can contribute to the developing nodule primordial has not been fully established. Now, on p. 3517, Ton Bisseling and colleagues unveil a detailed fate map of the origin of different cell types within the Medicago truncatula root nodule. By combining detailed and careful microscopy with promoter-reporter expression analyses, the authors analyse the fate of each root cell layer during nodule initiation. They show that the root inner cortex, endodermis and pericycle divide and transdifferentiate into about 16 cell layers that are located in the basal part of the nodule, whereas the middle cortex reprograms into the nodule meristem. The authors then use these data to re-evaluate previously published root nodule mutants, providing important contextual information for key developmental events during root nodule formation.

Out of the niche: exploring unknown pathways

In May 2014, approximately 200 stem cell scientists from all over world gathered near Copenhagen in Denmark to participate in ‘The Stem Cell Niche’, part of the Copenhagen Bioscience Conferences series. The meeting covered an array of different stem cell systems from pluripotent stem cells and germ cells to adult stem cells of the lung, liver, muscle, bone and many more. In addition to the stem cell niche, the meeting focused on a number of cutting edge topics such as cell fate transitions and lineage reprogramming, as well as stem cells in ageing and disease, including cancer. Here, Kateri Moore and Giulio Cossu describe the exciting work that was presented and some of the themes that emerged from this excellent meeting. See the Meeting Review on p. 3441

Roles for Hedgehog signaling in adult organ homeostasis and repair

JoynercroppedThe hedgehog (HH) pathway is well known for its mitogenic and morphogenic functions during development, and HH signaling continues in discrete populations of cells within many adult mammalian tissues. Here, Ralitsa Petrova and Alex Joyner review recently identified functions of HH in modulating the behavior of tissue-specific adult stem and progenitor cells during homeostasis, regeneration and disease. See the Review on p. 3445

 

piRNAs: from biogenesis to function

MiskacroppedSince their discovery less than a decade ago, Piwi-interacting RNAs (piRNAs) have been shown to repress transposable elements in the germline and, hence, have been at the forefront of research aimed at understanding the mechanisms that maintain germline integrity. More recently, roles for piRNAs in gene regulation have emerged. In their Review, Eva-Maria Weick and Eric Miska highlight recent advances made in understanding piRNA function, highlighting the divergent nature of piRNA biogenesis in different organisms, and discussing the mechanisms of piRNA action during transcriptional regulation and in transgenerational epigenetic inheritance. See the Review on p. 3458

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Categories: Research