The community site for and by
developmental and stem cell biologists

Friendly hello and a bit about stress & adult hippocampal neurogenesis

Posted by , on 27 June 2015

This is my first post for the Node, so I thought I would introduce myself a little bit…

I just finished my MSc in Experimental Psychology (Behavioural Neuroscience) and now I am striving towards becoming a science communicator. Although, I would like to share the research that I am interested in and was involved in, so here’s a glimpse:

I have an interest in the mechanisms underlying stress regulation, especially adult hippocampal neurogenesis. There is plenty of work published on the detrimental effects of stress on neurogenesis (See Review – Schoenfeld & Gould, 2012) in addition, at least one functional purpose for neurogenesis is stress regulation (Snyder et al., 2011). Chronic stress almost always suppresses neurogenesis (there are exceptions – see Hanson et al., 2011). However, acute stress is interesting in that there is conflicting evidence on its effects on neurogenesis. These differences may ultimately lie in the type of stressor used, although different results have manifested from the same protocol (Tanapat et al., 2001; Thomas et al., 2006).

Let’s take a step outside of the cellular/neuroscience world and into the more behavioural realm for just a moment:

I used an animal model for post traumatic stress disorder (PTSD) that was created by the late Bob Adamec which produces prolonged anxiety-like behaviour following the stressor. This model was unique in that very few labs in the world expose their rat subjects to an unprotected cat exposure (Adamec & Shallow, 1993)!

 

Image created by Catherine Lau

Image created by Catherine Lau

Much of the chronic stress research and neurogenesis work applies to stress and mood disorders. I wondered if there would be any effect on neurogenesis following a stressor that produces long lasting anxiety-like behaviour. In addition, an interesting review by Kheirbek et al., 2012 shows a potential link between PTSD and neurogenesis through pattern separation (differentiating highly similar contexts). In short, the review talks about how PTSD patients may have less newly born neurons available to differentiate similar episodes and therefore generalize, contributing to symptoms including the re-experience of the traumatic event in their mind. My results revealed that despite an evident stress response (as measured by corticosterone levels), neurogenesis was not different in the hippocampus between controls and predator stressed (Lau et al., manuscript in progress).

What’s happening? Here are some thoughts:

One immediate thought is adaptation, as a certain amount of stress is necessary to cope in our environments. But, how does this manifest in the brain? Kirby et al., 2013 reported an interesting result following acute stress (immobilization and foot shock). Instead of finding a decrease in neurogenesis, an increase in hippocampal neurogenesis was reported in the dorsal hippocampus due to increased secretion of astrocytic FGF2 (necessary proliferative factor for neural progenitor cells). This evidence demonstrates that acute stress may define a life-saving adaptation compared to long term pathology, by stimulating plasticity through increasing neurogenesis. Thus, new neurons in the hippocampus are perhaps needed during acute stress.

A difficult aspect to overcome in any experiment and also in mental health disorders is individual differences. The severity of the disorder may be different as well as how individuals respond to treatment. Some labs are tackling this problem by screening subjects before hand to group a vulnerable and resilient group. Rats displaying extreme behaviour in supposedly exploratory environments, such as the elevated plus maze (no time spent in open arms vs. closed arms) would be classified as the vulnerable group (Cohen et al., 2006).

In addition, there has also been interesting work done by Michael Meaney at McGill University attempting to look at the epigenetics behind depression and stress disorders. Individual differences were characterized by using the frequency of mother and pup interaction (licking/grooming behaviour). Offspring who had mothers giving a high amount of licking/grooming showed a reduced corticosterone response, as well as decreased startle and increased exploratory behaviour compared to those offspring who received less mother to pup interaction. By increasing grooming during their first week of life, rat mothers alter the DNA structure of the glucocorticoid receptor gene promoter in the hippocampus of their offspring (Meaney & Szyf, 2005). This evidence paves the way towards understanding risk factors in mental health, especially early life stressors and how they connect to mental disorders following childhood.

Although I am no longer involved in this area of research, I am trying my best to keep up to date with new experiments that will help elucidate the mechanisms underlying mental health disorders, such as depression and PTSD.

If anyone has interesting articles or thoughts about this, please let me know. Thank you!

 

References:

Adamec, R., & Shallow, T. (1993). Lasting effects on rodent anxiety of a single exposure to a cat Physiology & Behavior, 54 (1), 101-109 DOI: 10.1016/0031-9384(93)90050-P

Cohen, H., Zohar, J., Gidron, Y., Matar, M., Belkind, D., Loewenthal, U., Kozlovsky, N., & Kaplan, Z. (2006). Blunted HPA Axis Response to Stress Influences Susceptibility to Posttraumatic Stress Response in Rats Biological Psychiatry, 59 (12), 1208-1218 DOI: 10.1016/j.biopsych.2005.12.003

Hanson, N., Owens, M., Boss-Williams, K., Weiss, J., & Nemeroff, C. (2011). Several stressors fail to reduce adult hippocampal neurogenesis Psychoneuroendocrinology, 36 (10), 1520-1529 DOI: 10.1016/j.psyneuen.2011.04.006

Kheirbek, M., Klemenhagen, K., Sahay, A., & Hen, R. (2012). Neurogenesis and generalization: a new approach to stratify and treat anxiety disorders Nature Neuroscience, 15 (12), 1613-1620 DOI: 10.1038/nn.3262

Kirby, E., Muroy, S., Sun, W., Covarrubias, D., Leong, M., Barchas, L., & Kaufer, D. (2013). Acute stress enhances adult rat hippocampal neurogenesis and activation of newborn neurons via secreted astrocytic FGF2 eLife, 2 DOI: 10.7554/eLife.00362

Meaney MJ, & Szyf M (2005). Environmental programming of stress responses through DNA methylation: life at the interface between a dynamic environment and a fixed genome. Dialogues in clinical neuroscience, 7 (2), 103-123 PMID: 16262207

Schoenfeld, T., & Gould, E. (2012). Stress, stress hormones, and adult neurogenesis Experimental Neurology, 233 (1), 12-21 DOI: 10.1016/j.expneurol.2011.01.008

Snyder, J., Soumier, A., Brewer, M., Pickel, J., & Cameron, H. (2011). Adult hippocampal neurogenesis buffers stress responses and depressive behaviour Nature, 476 (7361), 458-461 DOI: 10.1038/nature10287

Tanapat, P., Hastings, N., Rydel, T., Galea, L., & Gould, E. (2001). Exposure to fox odor inhibits cell proliferation in the hippocampus of adult rats via an adrenal hormone-dependent mechanism The Journal of Comparative Neurology, 437 (4), 496-504 DOI: 10.1002/cne.1297

Thomas, R., Urban, J., & Peterson, D. (2006). Acute exposure to predator odor elicits a robust increase in corticosterone and a decrease in activity without altering proliferation in the adult rat hippocampus Experimental Neurology, 201 (2), 308-315 DOI: 10.1016/j.expneurol.2006.04.010

 

 

Thumbs up (2 votes)
Loading...

Tags:
Categories: Research

Navigate the archive

Use our Advanced Search tool to search and filter posts by date, category, tags and authors.

High school students blog about StemCellTalks

Posted by , on 27 June 2015

SCT-small groupsStemCellTalks is a Canadian high school outreach initiative that has been running in 7 Canadian cities since 2010. This symposium was established to facilitate knowledge transfer between academia and high school students pertaining to the science and practical ethics of stem cells. To date, over 500 graduate student and trainee volunteers have reached over 5000 high school students.

This year, the Vancouver chapter of StemCellTalks partnered with the biotechnology company STEMCELL Technologies Inc. to offer three talented student bloggers – Danielle Cohen, Julie Cui, and Ryan Scott – the chance to blog about their experience at StemCellTalks Vancouver. Furthermore, they won the opportunity to visit STEMCELL Technologies Inc.’s Vancouver headquarters on June 19, 2015. Over the next few weeks, you will be able to find their blog posts about StemCellTalks Vancouver appearing on Let’s Talk Science’s website Curiocity, as well as another version of this blog post at the stem cell blog Signals. We are happy to share Julie’s post here on the Node!

 

SCT-blogging 2015 winners
StemCellTalks Vancouver-STEMCELL Technologies Inc. Blogging Contest winners Ryan Scott (second from left) and Julie Cui (middle) along with StemCellTalks Vancouver organising committee member Courteney Lai (second from right) and STEMCELL Technologies Inc. Education specialists Raymond Lam (left) and Wendy Tan (right)

By Julie Cui (Lord Byng Secondary School, Vancouver, British Columbia, Canada)

Dr. Bruce Verchere pulled up a slide of a not-too-flattering depiction of Dr. Timothy Kieffer on the overhead screens and the room full of high school students erupted in laughter. It was a good-humored and very academic debate about stem cell vs. pig islet treatments for diabetes, I assure you, and seeing their passion for their field was one of those truly inspirational moments that I knew would stay with me for a long time.

8 o’clock earlier that Friday morning found me among a group of sleepy but excited high schoolers huddled in the foyer of the Pharmaceutical Sciences Building at UBC. It was the StemCellTalks Vancouver Symposium!

Armed with just pen, reading glasses, and basic Biology 12 knowledge of how stem cells worked in differentiating into different types of body cells, I was ready to absorb all the information I could about stem cell research findings and how they could be applied to diabetes treatment specifically. In the following hours, through the wonderfully informative talks by Dr. Fabio Rossi (UBC Biomedical Research Centre) and Dr. Francis Lynn (Child & Family Research Institute) and of course, the passionate debate between Dr. Bruce Verchere (Child & Family Research Institute) and Dr. Tim Kieffer (UBC Life Sciences Institute), we learned all about the different types of stem cells and how already-specialized body cells could be turned back into induced pluripotent stem cells, which could then specialize into a different type of body cell that we want. We also learned about alternatives to stem cell treatments of diabetes, including transplanting functioning donor islets and pig islets into patients with diabetes to help them produce the insulin they need to regulate their blood sugar levels. But I took away from StemCellTalks so much more than my new-gained knowledge of stem cell biology and stem cell-based treatments.

As a high school student, I find that we rarely have the chance to hear about professionals in science-related fields other than academic researchers. hile learning about academic research is very cool and inspiring in itself, it was the range of professional perspectives that we were exposed to at StemCellTalks that allowed me to see the bigger picture of the whole process of research and treatment development. Science professionals are not just the lab workers, but also the ethics board members, the regulation makers and the industry officials. For me, the various speakers’ perspectives really drove home the point that only through the combined efforts of all the different professionals involved can a treatment be discovered, tested, and eventually approved for clinical application. They encouraged me not to feel limited to just one idea of a career, but to continue exploring the many different types of careers in science, opening a whole other world of opportunity.

The passion of everyone at the symposium was so wonderful and inspiring as well. Although I am from the City of Vancouver, during the small group discussions, I met peers who had travelled from outside of Vancouver to be there, from as far away as Abbotsford and Vancouver Island. Many of them had personal connections to diabetes, and every one of them was eager to learn more and make a difference. It was such a pleasure to talk to like-minded peers and university mentors and feel that, in a few years, we could be part of this effort to improve stem cell treatments for diseases such as diabetes. I was genuinely inspired at the symposium, and am very eager to learn more about real-world applications of the treatments. As one of the winners for StemCellTalks’ blogging contest, I’m very excited to have the chance to visit STEMCELL Technologies Inc. to learn the role of such a successful biotechnology corporation in bringing treatments and technologies to life. I very much look forward to meeting the people involved in this biotechnology company, experiencing the real biotechnology industry work environment, and sharing that experience in a blog post with my peers and science-professionals-to-be, of course. In closing, I just wanted to say thank you to everyone who made the truly memorable experience that was StemCellTalks possible!

@StemCellTalks
#StemCellTalksVan

Thumbs up (1 votes)
Loading...

Tags: , ,
Categories: Events, Outreach

8th International Meeting of the LASDB

Posted by , on 25 June 2015

Join us for the 8th International Conference of the Latin American Society for Developmental Biology in the Port of Santos, SP, Brazil (October 20th-23rd).

We have a great line-up of speakers, a Genomic Editing and Analyses workshop, and a Comparative Embryology of Marine Invertebrate satellite course.

Abstract submission deadline is June 30th!!!  For more information check: http://lasdb2015.com/

 

Thumbs up (No Ratings Yet)
Loading...

Categories: Events, News

Conference Travel Grants: $1000 grants for biologists

Posted by , on 25 June 2015

We’re really excited to be providing travel grants to support life science researchers and would like to share the opportunity with you. As a lot of us on the Axol team have an academic research background in the life sciences, we are really aware of how important funding to attend conferences is. To help, we are offering 2 x $1000 travel grants to allow the recipients to attend a life science conference of their choice in order to advance and share their research knowledge. All we ask in exchange is that you provide a blog post about your meeting experience!

To be eligible you must be a PhD student or postdoctoral researcher at a university or other non-profit organisation performing life science award.

The deadline for the 2015/16 travel grant application is 30th June 2015. 

Find out how to apply here: http://www.axolbio.com/page/travel-grants

Thumbs up (No Ratings Yet)
Loading...

Categories: Funding

Post-doc Scholarship in Early Eye Development

Posted by , on 24 June 2015

Closing Date: 15 March 2021

Postdoc scholarship in Early Eye Development

at Umeå Centre for Molecular Medicine in the research group of Professor Lena Gunhaga

 

Umeå Centre for Molecular Medicine (UCMM) (www.ucmm.umu.se) is an interdisciplinary research centre with several research groups that study areas of biological and medical relevance. Localized in a tight environment of diverse biomedical laboratories, UCMM forms a creative and interactive unit for cutting edge biomedical research.

 

The scholarship is for 1 year with the possibility for extension.

Starting date: As soon as possible

 

Project description

The main focus is to understand the molecular mechanisms that control the early development of retina, RPE and lens cells, and the molecular interactions coordinating the development of these cell types in relation to their surroundings. The project will include both in vitro and in vivo eye developmental assays, in order to determine the individual roles of different signaling molecules involved in the early development of the eye. The applicant will use functional experiments such as cell and tissue cultures, as well as chick in ovo electroporations and analysing relevant mice mutants. The studies involve common developmental and molecular biology methods like; immunohistochemistry, in situ hybridization, and statistical analyses and image preparations.

 

Qualifications

The ideal candidate should be PhDs with a background in molecular or developmental biology, and passed an animal research course. A thorough theoretical and practical grounding in molecular and cell biology is a prerequisite. Practical experience with vertebrate embryonic model systems, molecular and cell biology methods and live imaging is an advantage. The applicant should be proficient in written and spoken English, and have good computer skills (Word, Photoshop, Excel). Of importance are also good organizational, independence, cooperation and problem solving skills.

 

 Other qualifications

An international postdoctoral training in the field of Molecular Biology or Developmental Biology is a merit.

  

Applications that are submitted electronically should consist of a single document in Word or PDF format and include the following information;

1) The applicants research interest, experience and suitability for the scholarship (max 1 page).

2) Methods that the applicant master (max 1 page).

3) Curriculum Vitae of the applicant including publication list.

4) Names and contact information of 2 referees, and stated professional

relationship with the applicant (max 1 page).

Your complete application marked with reference number FS 2.1.6-1047-15, should be sent to medel@diarie.umu.se to be received by  14 of August, 2015, at the latest.

We look forward to receiving your application!

 

For further information please contact: Professor Lena Gunhaga, 090-785 44 35, lena.gunhaga@umu.se

Thumbs up (No Ratings Yet)
Loading...

Categories: Jobs

Survey on Supplementary Information

Posted by , on 23 June 2015

At Development, and the other journals of The Company of Biologists, we are currently reviewing our policies and practises regarding Supplementary Information. As part of this, we are keen to find out your opinion on how Supplementary Information should be displayed, and what matters to you from a Supplementary Information policy viewpoint. To share you thoughts, please complete our short survey by clicking here. It shouldn’t take longer than 5 min and your feedback is essential for us to improve our service to authors and readers!

 

cmyk-grayscale

 

 

Thumbs up (2 votes)
Loading...

Categories: News

Signalling 2015 conference: abstract deadline fast approaching

Posted by , on 23 June 2015

Signalling 2015: Cellular Functions of Phosphoinositides and Inositol Phosphates
1—4 September 2015
Robinson College, Cambridge, UK

Join the Biochemical Society and FEBS in Robinson College, Cambridge, this SA171_image_160September for the Signalling 2015: Cellular Functions of Phosphoinositides and Inositol Phosphates conference. This meeting will bring together world-leading and early career scientists to discuss the latest research into the cellular functions of inositol phospholipids and phosphates.

Signalling 2015 is organized by Len Stephens (Babraham Institute), Phill Hawkins (Babraham Institute), Colin Taylor (University of Cambridge) and Peter Cullen (University of Bristol). The meeting will commemorate the retirement of Professor Robin Irvine, FRS. Sessions will be chaired by distinguished colleagues of Robin, including Professors Jim Putney and Bob Michell.

There are oral communication slots and flash poster presentations in the programme, which will be selected from student and early career poster abstracts. The abstract deadline ends 30 June so if you want to be in with a chance to present your work, click here.

The early bird registration deadline ends 3 August, register asap to avoid late fees.

Thumbs up (No Ratings Yet)
Loading...

Tags: , , , , , , , ,
Categories: Events

Development at the ISSCR

Posted by , on 23 June 2015

Tomorrow sees the start of the Annual ISSCR Meeting in Stockholm, Sweden. As one of the biggest conferences in the stem cell field – typically attracting around 4000 participants –  the ISSCR meeting showcases the latest and greatest in stem cell research and is a highlight on the Development team’s conference calendar. This year, both I (Katherine Brown, Development‘s Executive Editor) and Andrea Aguilar, our Reviews Editor for the stem cell field, will be attending the meeting.

Our publisher, The Company of Biologists, has a stand in the exhibition hall, and we’d be delighted to meet any Node readers attending the meeting, so please do drop by! We’ll be holding a small ‘meet the team’ session with coffee and snacks at our stand on Thursday afternoon (3-4pm), where Andrea and I will be happy to answer any questions you may have about the journal (or the Node), and you can also pick up some exclusive goodies from our stand – including our new, limited edition, ‘Stem Cells & Regeneration’ mugs!

IMG_2040

It promises to be an exciting meeting – if you can’t attend, you can keep up on Twitter with the hashtag #ISSCR2015. We hope to see you there!

Thumbs up (1 votes)
Loading...

Tags:
Categories: Events, News

Time travel for graduate students

Posted by , on 23 June 2015

Earlier this month, science & engineering graduate students at Washington University in St. Louis (WU) traveled in time. In the ballroom of the medical library, 70 students mingled with 15 young, professional scientists. At the first-annual Early Career Transitions Symposium, students got to fast-forward to learn what life might be like 5-10 years after graduation, and more importantly how to get there.

The symposium aimed to initiate discussion about the breadth of career opportunities for scientists by bringing together graduate students and local, young scientists. By inviting young scientists as our guests, the organizers targeted scientists who had recently made the transition from graduate school to their post-graduate career and whose experience would be most relevant to students nearing the end of graduate school.

 

Students and invited guests mingle at the Early Career Transitions Symposium at Washington University in St. Louis the evening of June 3, 2015.

Students and invited guests mingle at the Early Career Transitions Symposium at Washington University in St. Louis the evening of June 3, 2015. Photos credit: Pablo Tsukayama.

 

Anxiety among students about post-graduate opportunities is high, especially when students are considering leaving academia. With traditional, tenure-track positions stagnant, while Ph.D. awards continueto rise (Figure 1), trainees in scientific disciplines are taking control of their career paths. Nationally, groups like the Future of Research are starting the discussion about how science should work in the future. Others, like the National Science Policy Group, are advocating for increased research funding and giving students opportunities to explore a career in science policy.

 

awardsFigure 1. While the number of science and engineering Ph.D. awards has steadily increased since the 1980’s, the number of faculty positions has not kept pace. Reprinted with permission from Macmillian Publishers Ltd: Nature Biotechnology, Schillebeeckx, et al., 31, 938–941 copyright 2013 (doi:10.1038/nbt.2706).

 

But organization on the local level is essential for meaningful discussion about a student’s specific career path. That was the goal of student leaders organizing the Early Career Transitions Symposium.

The evening began with students and invited guests mixing and sitting down to dinner. Nathan Vanderkraats, Ph.D., was the keynote speaker. A computational scientist at Monsanto who did his post-graduate work at Washington University, Nathan urged students to follow their passion in their career. He encouraged each student to not “sell yourself short” – as graduate students in the sciences, you have a huge variety of skills, be confident of that and use it to your advantage. Finally, he cautioned not to let your scientific past determine your future. Simply because you have always been in a certain field, you should not feel limited to that field! Science is a way of thinking; bring your skills to bear on whatever the problem is you enjoy, whether it is at the bench or not. Decide where you want to be in your career and make that your reality.

 

Keynote speaker Nathan Vanderkraats advises graduate students to follow their passion.

Keynote speaker Nathan Vanderkraats advises graduate students to follow their passion.

 

Talking with the keynote speaker over dinner, biomedical graduate student, Erica Pehrsson, said she was struck by the different priorities in industry science; she learned “the focus is less on being the first to discover and publish, but instead on making sure that the result is reproducible and robust.” Graduate student Vasavi Sundaram said that she “felt hopeful about the career options post-graduation. It was very encouraging to learn that there are diverse job opportunities available. It stood out to me that the industrial sector accepts graduates with Ph.D. degrees even without a degree or experience in business development, marketing, etc.”

Graduate students at WU have been taking initiative to jump-start their careers for years. The BALSA Group, founded 2010, is a consulting firm staffed by graduate students and post-doctoral fellows. By participating in six-weeks long consulting projects, students get training in consulting and exposure to the local biotech community. Additionally, the BioEntrepreneurship Core organizes annual career panels and sponsors IdeaBounce competitions along with the WU Skandalaris Center for Interdisciplinary Innovation and Entrepreneurship for students to learn about the entrepreneurial scene and pitch their own ideas.

Lastly, ProSPER (WU Graduate Students Promoting Science Policy, Education, and Research) was established in 2012 and is a career development group with an emphasis on science policy and communication. ProSPER identifies areas of need and creates opportunities for graduate students to explore. We have sent students to Capitol Hill for advocacy days, organized field trips to local industry to talk about the importance of science communication, and regularly have scientists speak about their career paths and experiences in the science policy arena.

Of the Career Symposium, engineering graduate student Jake Meyer noted, “The event was great. I have known that I do not want to stay in academia after graduate school but was unsure of the paths, or even the options, out there to build my career. I learned about several different avenues to take and develop now so that I can make the move out of academia smoother as I approach graduation.”

At the end of the evening, students came away feeling motivated and encouraged about the future. Career panelists often recount stories about one specific connection that leads to a dream job – and this perspective can seem discouraging, especially if you feel your professional network is small. But realize the strength of your network! It only takes one connection to lead to an opportunity. At the Early Career Transitions Symposium, WU graduate students traveled in time, met their future scientist-selves, and were building their professional network.

 

Students and invited guests talk about careers for scientists over dinner.

Students glean career advice from invited guests over dinner.

Thumbs up (2 votes)
Loading...

Categories: Careers

From our sister journals- June 2015

Posted by , on 22 June 2015

Here is some developmental biology related content from other journals published by The Company of Biologists.

 

dmmlogo

 

 

Elucidating pulmonary hypoplasia in ciliopathies

Figure 5 Wnt5a interaction assaysCiliopathies are developmental disorders caused by mutations in components of the primary cilium (a microtubule-based mechanosensor organelle present in many mammalian cells), and are usually characterised by multi-organ abnormalities. Congenital lung malformation (pulmonary hypoplasia) often occurs, and is considered the leading cause of death in Meckel-Gruber syndrome (MKS), a lethal ciliopathy associated with mutations in the transmembrane protein 67 gene, Tmem67. To investigate mechanisms of pulmonary hypoplasia in MKS, Colin A. Johnson’s group characterised Tmem67–/– knockout mutant mice and used biochemical methods to further elucidate TMEM67 function. The group found that TMEM67 interacts with Wnt5a and receptor tyrosine kinase-like orphan receptor 2 (ROR2), two components of non-canonical Wnt signalling. Tmem67–/– embryos and pups manifest pulmonary hypoplasia phenotypes and, consistent with other available data, these are mediated by mutations of any component in the Wnt5a-TMEM67-ROR2 axis. Interestingly, pharmacological targeting of downstream effectors of this axis is able to rescue pulmonary abnormalities in cultured lungs from Tmem67–/– mice. These results implicate the dysregulation of the Wnt5a-TMEM67-ROR2 axis in ciliopathies and suggest that its downstream modulation can prevent pulmonary hypoplasia in these diseases. Read the paper here  (Open Access).

 

 

JCS

 

 

 

No sperm without miRNAs

Figure 2 DGCR8 DICER IF v3The microRNA (miRNA) pathway is known to be required for completion of murine spermatogenesis. However, the exact functions of miRNAs and the identity of their targets that are crucial for spermatogenesis are unclear. In their study, Paula Cohen, Andrew Grimson and colleagues unravel an essential role for miRNAs in the regulation of DNA damage repair to prevent sex chromosome defects during meiosis in males. The authors analysed mice with conditional knock-outs (cKO) of DGCR8 and DICER, which are essential for pri-miRNA and pre-miRNA processing, respectively, and found abnormal pairings of sex chromosomes or their fusion to autosomes. They also showed that levels of ataxia telengiectasia mutated (ATM) kinase were elevated in both cKO lines and that the phosphorylated ATM substrate mediator of DNA damage checkpoint-1 (MDC1) was mislocalised in DICER KO spermatozoa. As shown here, the Atm 3ʹUTR functionally interacted with miRNA (miR)-18, miR-16 and miR-183, suggesting a role of these miRNAs in the regulation of spermatogenesis. Importantly, the authors demonstrated that the DNA damage repair protein RNF8, whose localisation is partly controlled by ATM-MDC1 signalling, was redistributed from sex chromosomes to autosomes. Taken together, these results indicate that ATM is regulated by miRNAs to ensure the proper localisation of its substrates that are involved in maintaining chromosomal stability during spermatogenesis. Read the paper here (Open Access).

 

Dendrite arborisation – it has to be NudE

JCS170316F6Dynein and kinesin molecular motors play important roles in neuronal morphogenesis, but the precise mechanism of their action is still unclear. Nuclear distribution E (NudE) proteins are involved in neuronal proliferation and migration, but they are also known to function as dynein cofactors and, as such, could be involved in neurite outgrowth. Taking advantage of the fact that only one NudE protein is present in Drosophila melanogaster, Jill Wildonger and colleagues investigate the role of NudE in dendrite arborisation of class IV neurons in 3rd instar larvae. They found that NudE colocalised with vesicular cargo and Golgi outposts in wild-type larvae, whereas its depletion resulted in shorter dendrites with fewer branches, increased microtubule dynamics and altered microtubule polarisation in the axon. Confirming a role for NudE in dendritic arborisation as a dynein cofactor, NudE ablation also enhanced the severity of a mild dynein-mutant phenotype. The authors found that the C-terminus of NudE was inhibitory to its activity in promoting dendrite arborisation, as a C-terminus-deletion mutant rescued the dendrite arborisation defect in NudE-depleted neurons to a greater extent than the full-length protein. Importantly, overexpression of another dynein cofactor, Lis1, rescued NudE neurons, but no rescue was observed when NudE was prevented from interacting with Lis1. Based on their results, the authors conclude that the function of NudE in promoting dendrite growth is to stabilise the dynein–Lis1 interaction. Read the paper here (Open Access).

 

Role of traction force in definitive endoderm specification

Figure2Differentiation of embryonic stem cells (ESCs) into definitive endoderm requires signalling by both growth factors – such as activin A and Wnt3a – and extracellular matrix (ECM) components – such as fibronectin (FN) and laminin. Although ESCs do both, exerting traction forces and responding to the mechanical properties of the ECM, little is currently known about how soluble factors induce biochemical and physical changes in the ESCs and their associated matrix, when added to differentiate ESCs. Here, Adam Engler and colleagues used a force-sensitive FN matrix assay in mouse ESCs to understand the crosstalk between mechanical factors and chemical signals in ESCs and the ECM in directing developmental cues. Addition of the myosin inhibitor blebbistatin inhibited ESC differentiation, indicating that traction forces are necessary for the formation of definitive endoderm. This effect is possibly exerted through TGF-β signalling because this treatment transiently prevented the nuclear translocation of the TGF-β effector phosphorylated SMAD2. The authors then showed that extracellular laminin-111 regulated differentiation; its binding to α3β1-integrin inhibited the SMAD2 inhibitor SMAD7 and also decreased FN-induced matrix strain that acts through α5β1-integrin. Taken together, this study shows that soluble factors that induce ESC differentiation activate traction forces, which – in turn – utilise integrins and ECM remodelling to feedback and support growth-factor-activated signalling cascades. Read the paper here.

 

 

JEB

 

 

 

 

Pipefish fathers do not boost embryos’ oxygen

JEB125195The pipefish brood pouch presents a unique mode of parental care that enables males to protect, osmoregulate and nourish the developing young. Lower availability of oxygen in water was believed to naturally limit the size of fish eggs and, as pipefish eggs are relatively large for the fish’s size, it was assumed that the males somehow provided an abundant supply of oxygen. Using a very fine O2 probe, Braga Goncalves and colleagues assessed the extent to which males of the broad-nosed pipefish oxygenate the developing embryos and are able to maintain pouch fluid O2 levels when brooding in high and low oxygen concentration. Their results show that male pipefish are unable to boost the oxygen supply that they provide to their precious cargo and the mystery of why pipefish eggs are so large remains. Read the paper here.

 

 

Bubbles create cosy environment for developing embryos

JEB112235Some amphibians breed in terrestrial environments and make bubble nests to lay their eggs in. It was long assumed that the bubbles helped protect developing eggs from predators, reduced egg dehydration and improved the oxygen supply to the developing embryos. Steve Portugal highlights a paper by Méndez-Narváez and colleagues recently published in Physiological and Biochemical Zoology, identifying an additional role for terrestial bubble nests- insulating the developing embryos from extreme fluctuations in ambient temperatures. Read this Outside JEB feature here.

 

 

Thumbs up (No Ratings Yet)
Loading...

Tags: , , , ,
Categories: Research