Here are the highlights from the new issue of Development:

A new mechanism in ESC lineage priming

Histone demethylases have recognized roles in the control of gene expression during development and disease, and are typically associated with the remodelling of the chromatin environment. Jmjd2/Kdm4 H3K9-demethylases cooperate in promoting mouse embryonic stem cell (ESC) identity, but their specific roles during the exit from pluripotency are still unclear. In this issue (p. 567), Véronique Azuara and colleagues uncover a previously unrecognized functional link between Jmjd2c recruitment to lineage-specific enhancers and ESC priming for differentiation. The authors show that Jmjd2c is required for the proper assembly of mediator-cohesin complexes at lineage-specific enhancer regions, and that differentiation is stalled at an early post-implantation epiblast-like stage in both Jmjd2c-knockout and Jmjd2c-knockdown ESCs. Interestingly, Jmjd2c-deficient cells were still able to differentiate towards extra-embryonic endoderm-like cells. At the chromosomal level, the authors showed how Jmjd2c-bound enhancers are co-occupied by the H3K9-methyltransferase G9a/Ehmt2 independently of its canonical H3K9-modifying activity, and suggest that Jmjd2c-G9a co-occupancy might facilitate the loading of Med1 and Smc1a molecules. This study is significant and novel as it reveals a new mechanism for the regulation of lineage priming in ESCs via Jmjd2c-mediated stabilisation of essential protein complex assembly at enhancers.

Tick tock goes the segmentation clock

Somitogenesis is the process by which the somites, blocks of mesoderm that give rise to tissues such as the vertebrae, skeletal muscle, cartilage, tendons and skin, are formed. The process occurs under the control of a ‘segmentation clock’: the oscillatory expression of a number of genes and proteins that control cell commitment. The protein paraxial protocadherin (PAPC) is a protocadherin that has been implicated in paraxial mesoderm segmentation; however, the way in which PAPC controls somite formation remains unclear. Now, on p. 664, Olivier Pourquié and colleagues investigate the role of PAPC in chick and mouse somite boundary formation, and demonstrate an entirely novel mechanism for periodic somite formation through the regulated endocytosis of N-cadherin (CDH2). The authors first show that PAPC is cyclically expressed downstream of the segmentation clock, and that PAPC expression colocalizes with CDH2 in the rostral half of the forming somite. In ovo overexpression of the short PAPC isoform in the presomitic mesoderm disrupts apical accumulation of CDH2 and interferes with proper somite morphogenesis. Mechanistically, the authors show how PAPC regulates the endocytosis of CDH2 in the anterior compartment of the forming somite, that is, in regions that have not yet epithelialized. In this way, PAPC regulates the segmental de-adhesion of the somites, which is crucial for their subsequent formation.

p53⁺ cells drive in vivo cardiomyocyte expansion

The mammalian heart has a limited capacity to regenerate. Under certain conditions, however, cardiomyocyte proliferation has been observed, for example in resected neonatal hearts and in response to certain cytokine treatments. Nevertheless, the extent to which cardiomyocyte proliferation occurs both in steady state and after injury in the postnatal mouse is hotly debated, as studies are limited by a lack of reliable genetic tracing tools. Now, on p. 580, Zhongzhou Yang and colleagues use a p53-based genetic tracing system to investigate postnatal cardiomyocyte proliferation and heart regeneration through neonatal, adolescent and adult stages. The authors observed clonal expansion of p53⁺ cardiomyocytes in the neonatal heart, as well as in pre-adolescent and adult hearts. Interestingly, some of the labeled cardiomyocytes also formed larger clusters if given a longer tracing time, suggestive of a selectively long-lasting proliferative potential. The authors also investigated cardiomyocyte proliferation after cryo-injury and showed that p53⁺ cardiomyocytes exhibit cytomembrane localization of the sarcomeric protein cTnT during heart regeneration, consistent with previous studies. Finally, the authors demonstrated that the p53 genetic labeling system reliably traced proliferating cardiomyocytes following not only in cryo-injury, but also in two additional types of cardiac injury models in neonatal mice. This study reveals the specific lineage contribution to mammalian cardiac repair and provides evidence for the heterogeneity of cardiomyocytes in mammalian heart.

PLUS:

Auxin 2016: a burst of auxin in the warm south of China

Auxin – a key plant hormone – plays a prominent role in regulating plant developmental processes, and delineating its role is therefore the subject of intensive investigation. In their Meeting Review, Teva Vernoux and Stéphanie Robert discuss discuss new insights into auxin-mediated signalling that were presented at the Auxin 2016 meeting, which was held in Sanya, China, in October 2016.

Metabolic remodeling during the loss and acquisition of pluripotency

Cellular metabolism plays a vital role in development, beyond the simple production of energy, and may be involved in the regulation of cell fate. In their Review article, Julie Mathieu and Hannele Ruohola-Baker review the metabolic changes that occur during the transitions between different pluripotent states, both in vitro and in vivo, and discuss the extent to which distinct metabolites might regulate these transitions.

Neural tube closure: cellular, molecular and biomechanical mechanisms

The process of neural tube closure is complex and involves cellular events such as convergent extension, apical constriction and interkinetic nuclear migration, as well as precise molecular control via the non-canonical Wnt/planar cell polarity pathway, Shh/BMP signalling, and the transcription factors Grhl2/3, Pax3, Cdx2 and Zic2. More recently, biomechanical inputs into neural tube morphogenesis have also been identified. In their Review article, Andrew Copp and colleagues review these cellular, molecular and biomechanical mechanisms involved in neural tube closure.

(No Ratings Yet)

Loading...

We are seeking to recruit a postdoctoral fellow to develop and apply high resolution light sheet microscopy in order to image cytoskeletal networks and adhesion complexes in developing embryos (e.g. Drosophila). We have recently developed a light sheet microscope for fast 3D imaging and we aim at including a new illumination scheme to achieve higher resolution and single molecule detection. The recruited postdoc will also develop new image analysis tools to analyze the generated high resolution data.

The candidates should have experience in computational image analysis and/or optical engineering (including software engineering for machine control).

The postdoc will benefit from an interdisciplinary environment with expertise in imaging, optical engineering, physics and cell developmental biology (Labex Inform, IBDM)

The postdoctoral fellowship is offered for a period of two years.

Applicants should send a CV, names of two referees, and a short outline of their research interests to P.-F. Lenne and T. Lecuit.

(No Ratings Yet)

Loading...

PhD Studentship

Live imaging of mouse peri- and post-implantation morphogenesis

Fixed-term:  The funds for this post are available for three years.

ImageInLife is a Marie Skłodowska-Curie Innovative Training Network (MSCA-ITN)  funded by the European Commission Horizon 2020 programme and focused on the training of European experts in multilevel bio-imaging, analysis and modelling of vertebrate development and disease.

In the context of the ImageInLife network, the Department of Physiology, Development and Neuroscience (PDN), University of Cambridge, has a vacancy for one Early Stage Researcher (ESR, PhD student) on the project detailed below.

Project description: Live imaging of mouse peri- and post-implantation morphogenesis

The ESR will work in the group of Prof. Magdalena Zernicka-Goetz with Drs Neophytos Christodoulou and Matteo Molè as co-supervisors. The project aims to uncover the morphogenetic events shaping the mouse embryo during implantation development in the synthetic and natural environment. The ESR will use the well-established ex-vivo culture system developed in the host laboratory, in combination with transgenic fluorescent reporter mouse lines and advanced confocal and multiphoton microscopy. Additionally, 4D cell motion and lineage tracking analysis will be performed to characterise how single cell behavior contributes to tissue wide morphogenetic  events.

Applicants should hold a degree in biology, biophysics, or biomedical sciences and must comply with the eligibility criteria and transnational mobility rules for MSCA-ITN:

• Early-stage researcher (ESR) will be appointed for three years as Marie Skłodowska-Curie Fellow. The Fellowship is offered in conjunction with a PhD position in the PDN, University of Cambridge and will be subject to the Fellow satisfying the University’s admissions requirements. At the time of recruitment, the ESR shall be in the first four years (full-time equivalent research experience) of his/her research career and have not been awarded a doctoral degree.
• Full-Time Equivalent Research Experience is measured from the date when the researcher obtained the degree entitling him/her to embark on a doctorate (either in the country in which the degree was obtained or in the country in which the researcher is recruited or seconded), even if a doctorate was never started or envisaged.
• Trans-national mobility (i.e. move from one country to another) is an essential requirement of MSCA-ITN. The ESR can be of any nationality. At the time of recruitment by the host organisation, he/she must not have resided or carried out his/her main activity (work, studies, etc) in the country of the host organisation for more than 12 months in the three years immediately before the reference date. Compulsory national service and/or short stays such as holidays are not taken into account.

The ESR will be employed at the host institute by a contract with full social security coverage. He/She will receive a salary of £35,000 per annum augmented by a mobility allowance of £5,600 per annum in line with the EC rules for Marie Skłodowska-Curie grant holders. The ESR will be liable to pay his/her fees (see www.graduate.study.cam.ac.uk/finance). The appointment will be made on educational background, research experience, fluency in spoken and written English, and motivation to take part in and contribute to the research and training programme of the ImageInLife consortium. Applications, in English, should include a covering letter, CV, detailed academic transcripts and two reference letters, which are all to be submitted through the on-line application system at https://www.imageinlife-application.eu. Additionally, please submit the same application documents by email to Drs Christodoulou (nc480@cam.ac.uk) and Mole (mam238@cam.ac.uk).

ImageInLife strives to recruit between 40-60% female researchers. For more information contact Prof. Magdalena Zernicka-Goetz (mz205@cam.ac.uk).

The application deadline is 15 March 2017.

(No Ratings Yet)

Loading...

Decoding the network logic for resetting pluripotency – Collaborative Stem Cell Research PhD Studentship with Microsoft Research – re-advertised, revised closing date 31^st March 2017

Outline Project Description:

• Interdisciplinary project at the interface of stem cell research and computational modelling
• Delineation of network trajectories for cellular reprogramming at single cell resolution
• Combination of wet lab research with logical modelling
• Collaboration between the laboratory of Prof. Austin Smith and Microsoft Research Cambridge

The Smith Group at the Medical Research Council Wellcome Trust Stem Cell Institute in Cambridge in partnership with the Computational Biology Group at Microsoft Research offers an exciting interdisciplinary 4-year PhD studentship commencing October 2017.
The pluripotent ground state of embryonic stem cells (ESCs) is governed by a self-reinforcing interaction network of transcription factors (Dunn et al, Science 2014). Combinations of factors within this network can induce somatic cells to acquire pluripotency, a process called molecular reprogramming (Takahashi and Yamanaka, Cell, 2006). Experimental and computational efforts have led to circuitry mapping of the key players in maintenance of the ESC state. However, how this molecular circuitry is launched and fully connected during reprogramming remains unclear.

This project is a cross-disciplinary investigation to address systematically how cells transit to the pluripotent ESC state at the molecular network level. The multi-step, heterogeneous and asynchronous nature of the reprogramming process presents technical challenges. This project is designed to overcome these challenges by using a minimal reprogramming system and integrating quantitative single-cell gene expression profiling at defined reprogramming stages with computational network synthesis and modelling. This approach will transform a temporal series of single-cell snapshots of network status into reconfiguring network trajectories. Predictions formulated from the synthesised trajectories will be tested experimentally and the results used for iterative refinement of the model set.
As part of the BBSRC doctoral training programme, this 4-year PhD contains tailored training courses in the first six months of the studentship. In addition, a key element of this project is that the student will spend three months at Microsoft Research Cambridge, under the supervision of our collaborator, Dr Sara-Jane Dunn, to develop wider training and skills.
For further details about our group and the institute, please visit:http://www.stemcells.cam.ac.uk/ 

Funding Notes

UK and EEA students who have, or are expecting to attain, at least an upper second class honours degree (or equivalent) in relevant biological subjects are invited to apply. The interdisciplinary nature of the project means that we welcome applications from students with mathematical and computing experience who are interested in using their skills to address biological questions.

Application details are available at http://www.stemcells.cam.ac.uk/study/otheropportunities/#BBSRC. Please ask your referees to submit references directly to the SCI Graduate Administrator: sci-phd@stemcells.cam.ac.uk, using “BBSRCiCASE student reference” in the subject header. The deadline is 31^st March 2017 and shortlisted candidates will be interviewed in April. Please note: this studentship is being re-advertised. Previous applicants need not apply.

References

Dunn, S. J., Martello, G., Yordanov, B., Emmott, S. & Smith, A. G. Defining an essential transcription factor program for naïve pluripotency. Science 344, 1156-1160, (2014).
Martello, G. & Smith, A. The nature of embryonic stem cells. Annu Rev Cell Dev Biol 30, 647-675, (2014).
Yordanov, B., Dunn, S.-J., Kugler, H., Smith, A., Martello, G. & Emmott, S. A method to identify and analyze biological programs through automated reasoning. Npj Systems Biology And Applications 2, 16010, (2016)

(No Ratings Yet)

Loading...

The use of chimaeras to study developmental mechanisms: from lineage tracing to disease models

Under the sponsorship of the Anne McLaren Memorial Trust Fund and The Company of Biologists, the BSDB Autumn meeting organised by Jenny Nichols and Tristan Rodriguez took place in the Pollock Halls at the University of Edinburgh. The topic this year was: ‘Chimaeras and their use in studying developmental processes and disease models’. Chimaeras are made of cells from two or more different organisms of the same or different species. Since their first conception, chimaeras have been an essential tool to dissect cellular potential and are used to address a large number of questions in developmental biology using a variety of different model organisms, from plants to vertebrates.

(2 votes)

Loading...

A recent publication in Developmental Biology by (Armit et al., 2017) describes how the TRACER dataset can be spatially compared with in situ hybridisation gene expression profiles.

• The TRACER dataset of transposon-associated regulatory sensors (Chen et al., 2013) utilises Sleeping Beauty lacZ transposons that have been randomly integrated into the mouse genome
• Hundreds of insertions have been mapped to specific genomic positions, and the corresponding regulatory potential is documented through lacZ imaging of E11.5 wholemount mouse embryos
• Through spatial mapping of the lacZ expression patterns, the EMAGE gene expression database enables co-localisation and co-expression of regulatory elements to be explored computationally
• Spatial mapping additionally enables rapid identification of cis-regulatory elements that are expressed in a region of interest in the mouse embryo

Click here to access the spatially mapped TRACER dataset in EMAGE.

References

Armit C, Richardson L, Venkataraman S, Graham L, Burton N, Hill B, Yang Y, Baldock RA. eMouseAtlas: An atlas-based resource for understanding mammalian embryogenesis, Developmental Biology, Available online 2 February 2017, ISSN 0012-1606, http://dx.doi.org/10.1016/j.ydbio.2017.01.023

Chen, C-K, Symmons O, Uslu VV, Tsujimura T, Ruf S, Smedley D, Spitz F. TRACER: a resource to study the regulatory architecture of the mouse genome. BMC Genomics 14 (2013), p. 215, https://dx.doi.org/10.1186/1471-2164-14-215

(No Ratings Yet)

Loading...

Young Embryologist Network 9th Annual Conference.

9th May 2017 at the Institute of Child Health, UCL, London.

This year, YEN is honoured to have Dr Darren Gilmour from
EMBL Heidelberg present the Sammy Lee Memorial Lecture. We are also pleased to host two invited speakers, Dr Karen Liu (King’s College London), and Professor Michael Stumpf (Imperial College London). As well as three abstract-selected talk sessions and a poster session, we are holding a Q&A panel on the topic of science communication with Jenny Jopson and Jonathan Wood from the Francis Crick institute.

We are looking for talks and posters from PhD students and Post-docs on Evo-Devo, Stem Cell, and Developmental Biology, from both experimental studies and theoretical modelling.

The deadline for abstract submission is midnight on 9th of April 2017.

(No Ratings Yet)

Loading...

Radial glial cells are multipotent progenitors in the developing vertebrate brain. At their apical interface with the ventricular cavity around which the brain forms, they bear a primary cilium, a signalling and sensory organelle crucial for proper brain development. Today’s paper, from a recent issue of Development, addresses the link between these primary cilia and brain morphogenesis. We caught up with first author Philippe Foerster and group leader Nathalie Spassky of the Institut de Biologie de l’Ecole Normale Supérieure in Paris.

So Nathalie, can you tell us your scientific biography and what questions your lab is interested in?

NS I am a developmental neurobiologist. For my PhD that I obtained in Paris, I studied oligodendrocyte development in vertebrates. I then studied the contribution of multiciliated ependymal cells to adult neurogenesis as a post-doctoral fellow at UCSF. In 2010, I set up my own lab at the Institut de Biologie de l’Ecole Normale Supérieure, in Paris, where we develop multidisciplinary approaches to decipher the development and functions of ciliated cells in the mammalian brain.

What is Paris like for cell and developmental biology?

NS A highly stimulating environment with a great community of labs working on different aspects of cilia biology and brain development. The approaches range from cell biology to genetics and use a large variety of models (Xenopus, zebrafish, planarian, paramecium and rodents).

And Philippe, how did you come to join Nathalie’s lab?

PF I was a student in the Master 2 program in stem cell biology at the Pierre and Marie Curie University (UPMC) in Paris. I joined Nathalie Spassky’s lab for my Master 2 internship, because I was looking for a lab working on embryonic neural stem cells. I already had some experience in that field. What I immediately liked in Nathalie was her ability to mix disciplines (such as physics and biology) to approach things differently. This allowed me to contribute my computer skills to the lab and use them, especially for the analysis of apical surface segmentation.

What was known about the role of primary cilia in brain morphogenesis before your current work?

NS & PF The primary cilium has mainly been studied during early stages of brain development. A number of labs have shown that the primary cilium is crucial for telencephalic patterning and morphogenesis. The primary cilium is also a well known transducer of Sonic Hedgehog signalling.

Can you give us the key results of your paper in a paragraph?

NS & PF Radial glial cells are bipolar cells found throughout the brain during embryonic development. These cells undergo morphological changes during the cell cycle and brain development. We have shown that the enlargement of their apical domain during development is regulated through the primary cilium and the mTORC1 pathway. Although the phenotype observed in the ciliary mutants does not lead to major cortical defects during embryonic development, it initiates postnatal hydrocephaly and might be responsible for major postnatal brain dysfunctions. This possibility is currently being tested in the lab.

Why do you think having a larger apical surface interferes with normal radial glial cell development?

NS & PF Enlargement of the apical surface of radial glial cells affects the orientation of the mitotic spindle, maybe because radial microtubules do not attach correctly to the cell cortex during mitosis. Misorientation of the mitotic spindle leads directly to an increased number of basal progenitors and defects in cortical development, such as an alteration of the number of differentiated cells. Interestingly, we show that this phenotype can be rescued by treatment with the mTORC1 inhibitor rapamycin, suggesting that the apical domain is enlarged in cilia mutants through transduction of the mTORC1 pathway by the primary cilium. Further investigations are needed to determine the molecular mechanisms and whether they involves upregulation of protein synthesis.

Do you have an idea what is upstream and downstream of mTORC1 in this system?

NS & PF We would love to know! We think that the upstream signals could be biochemical and/or mechanical cues that would be sensed by the primary cilia. This was the reason why we generated mutants for the mechanosensory protein polycystic kidney disease 1 (Pkd1). However, no difference in the surface area of radial glial cell apical domains was observed in Pkd1 conditional mutants. It would thus be interesting to study how other mechanical stress pathways might be involved in these regulations. Similarly, the downstream signals should be the focus of future studies as they might involve specific molecular cascades and cytoskeletal modifications that would interfere with cell fate and brain development.

What significance does your work have for our understanding of ciliopathies?

NS & PF Brain malformations are often observed in ciliopathies, although their etiology is still not well characterised. We show that primary cilia defects lead to ventricular enlargement (ventriculomegaly), which initiates postnatal hydrocephalus and might be responsible for major brain dysfunctions that still need to be characterized.

When doing the research, was there a particularly exciting result or eureka moment that has stayed with you?

PF It took me many hours to map the brain ventricle apical surface, which required tonnes of confocal images and lots of adjustments of the segmentation program. My eureka moment arrived when I saw for the first time the colour-coded area map of the apical surface of a Nestin-K3A^cKO embryos at E14.5. When I saw lots of enlarged apical domains in Nestin-K3A^cKO embryos, I realised that this tiny antenna could play a role in the development of this phenotype. I knew that we were on the right track when we obtained the western blot results showing the implication of the mTOR pathway and rescue with the mTORC1 inhibitor rapamycin. This pathway was already known to be involved in the proper control of cell size.

And what about the flipside: any moments of frustration or despair?

PF It took at least a year to breed the Nestin-K3A^cKO (and IFT88^cKO) mutants. At the end of my first year of thesis work, we had many problems with one of the Nestin cre line that we were using, because it unexpectedly displayed ectopic Cre expression. This was very stressful because we had to start the mouse breeding and the phenotype analysis all over again. It took another year to overcome these difficulties, but this time we double checked the cre recombinase expression before drawing conclusions!

Finally Philippe, what are your plans following this work?

PF I defended my thesis in September 2014. I then continued my career but in the world of IT while keeping in touch with the biomedical field. I have been working for more than 2 years now in an IT service company that is dedicated to clinical research.

And where next for the Spassky lab?

NS We are addressing several questions related to the molecular and cellular mechanisms of neural stem cell fate choices, multiciliated ependymal cell development and brain ventricular morphogenesis. To be continued…!!

Philippe Foerster, Marie Daclin, Shihavuddin Asm, Marion Faucourt, Alessandra Boletta, Auguste Genovesio, Nathalie Spassky. mTORC1 signaling and primary cilia are required for brain ventricle morphogenesis. Development. 144:201-210

(13 votes)

Loading...

“For the harmony of the world is made manifest in Form and Number, and the heart and soul and all the poetry of Natural Philosophy are embodied in the concept of mathematical beauty.”

D’Arcy Thompson’s On Growth and Form, which celebrates its centenary this year, is one of the key works at the intersection of science and the imagination. Hailed as “the greatest work of prose in twentieth century science”, it is a book that has inspired scientists, artists and thinkers as diverse as Alan Turing, C. H. Waddington, Claude Lévi Strauss, Jackson Pollock and Norman Foster. It pioneered the science of biomathematics, and has had a profound influence in art, architecture, anthropology, geography, cybernetics and many other fields. This year we celebrate the book’s centenary with a range of conferences, exhibitions and other happenings around the world, all of which are being promoted through the website www.ongrowthandform.org

D’Arcy Wentworth Thompson was born in Edinburgh in 1860. He took up the first chair of biology at University College, Dundee (now the University of Dundee) in 1885, aged just 24, and spent much of his first decade building up an extensive Zoology Museum. In 1889 he wrote to one of his students, “I have taken to Mathematics, and believe I have discovered some unsuspected wonders in regard to the Spirals of the Foraminifera!”

D’Arcy became convinced that the laws of mathematics could be used to explain the growth and form of living organisms. This was a controversial topic and it wasn’t until 1917 that he finally published his ideas in On Growth and Form. Nature called it “at once substantial and stately… It is like one of Darwin’s books, well-considered, patiently wrought-out, learned and cautious.” The comparison to Darwin is interesting, given that many saw the book as arguing against Darwinian evolution. D’Arcy said, “where it undoubtedly runs counter to conventional Darwinism, I do not rub this in, but leave the reader to draw the obvious moral for himself.” The “obvious moral” was that Darwin was wrong in seeing the evolution of form purely as a gradual process dictated by natural selection. D’Arcy’s Theory of Transformations, the most famous and radical chapter in the book, proposed that physical forces could cause a transformation from one species into another based on mathematical principles. Through his iconic transformation diagrams, D’Arcy demonstrated that laws of growth rather than evolution could be used to explain the different forms of related species.

For much of the 20th century, D’Arcy’s ideas ran counter to biology’s increasing focus on evolution and genetics but a number of developmental biologists such as C H Waddington continued to champion his work. He also found followers in other fields, such as the father of modern computing, Alan Turing.

By the 1980s, the growth of evolutionary-developmental biology had caused D’Arcy’s work to be revisited by many that had hitherto dismissed it. Richard Dawkins has noted that “It is one of the minor tragedies of biology that D’Arcy Thompson died just before the computer age, for almost every page of his great book cries out for a computer.” Technological developments have indeed transformed the scientific relevance of D’Arcy’s work, and new mathematical modelling techniques have allowed his theories to be tested scientifically for the first time. Today even arch-geneticists like Dawkins freely acknowledge D’Arcy’s significance.

D’Arcy has also been described as having a greater impact on the worlds of art and architecture than any other scientist of the 20th century. On Growth and Form inspired architects and engineers from Le Corbusier and Mies van der Rohe to Norman Foster and Cecil Balmond. Henry Moore, Richard Hamilton, Eduardo Paolozzi and Salvador Dali are among the artists known to have read and drawn on the book.

Although D’Arcy’s original museum was demolished in the 1950s, his surviving collection is now displayed in the D’Arcy Thompson Zoology Museum at the University of Dundee, which is used not just in teaching life sciences but also by students of fine art, design, philosophy, creative writing and other subjects. The museum is open to the public regularly over the summer and for special events and activities throughout the year.

D’Arcy Thompson has recently been described as “the most important figure in the future of biology” and we are determined to ensure his work continues to exert a significant influence for many years to come. The centenary of On Growth and Form is being celebrated with a major conference and exhibition in Dundee in October (call for papers to follow soon!), and many other activities both here and around the world. Visit www.ongrowthandform.org to find out more.

(5 votes)

Loading...

New DMDD data released on Expression Atlas reveals the effect of single gene knockouts on the expression of all other genes in the mouse genome. The gene expression profiles of 11 knockout lines have been derived from whole embryos harvested at E9.5, and the results can be compared with wild-type controls using an interactive online tool. Users can investigate which genes are differentially expressed as a result of a gene knockout, with the potential to uncover genes with similar roles or compensatory effects when a related gene is knocked out.

Data for additional lines will be released throughout 2017. The ultimate goal is to bring these molecular phenotypes together with the morphological phenotypes that have already been derived by the DMDD programme, to offer new insights about the effects of gene knockout on embryo development.

THE GENOMIC EFFECTS OF Ssr2 KNOCKOUT

The knockout of Ssr2 in the mouse was found to affect the expression level of 325 genes in total, and this is one of the 11 new datasets that can be explored in Expression Atlas.

The differential expression of each gene is described using the log₂ fold change – a measure that describes the ratio of gene expression in the knockout to the level of gene expression in a wild-type control. A negative fold change (shown in blue in the image below) means that the gene was expressed at a lower level in the mutant. A positive fold change (shown in red in the image below) means that the gene was expressed at a higher level in the mutant.

The interactive tool in Expression Atlas allows different cut-offs to be applied to the fold change, so the genes displayed can be restricted to those with a large differential expression. The image above shows the 8 genes with a fold change greater than 0.4 as a result of knocking out the gene Ssr2.

The tool can also be used to visualise the data in graphical form. The plot below shows the fold change for each gene, allowing the user to quickly ascertain the extent to which a gene knockout caused differential expression of other genes. All 325 genes considered to have a significant change in the level of gene expression are plotted in red, with the rest shown in grey.

The full list of lines with data currently available is: 1700007K13Rik, 4933434E20Rik, Adamts3, Anks6, Camsap3, Cnot4, Cyp11a1, Mir96, Otud7b, Pdzk1 and Ssr2.

The full dataset for any line can be downloaded for further analysis, while the individual line pages on Expression Atlas integrate the DMDD data with other pre-existing data, in cases where a gene has already been shown to alter expression.

(No Ratings Yet)

Loading...