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Bénédicte Sanson – Winner of the 2019 Cheryll Tickle Medal.
In 2016, the BSDB introduced the Cheryll Tickle Medal, which is being awarded annually to a mid-career, female scientist for her outstanding achievements in the field of Developmental Biology.
The BSDB is proud to announce the 2019 awardee Bénédicte Sanson. Due to family commitments, Bénédicte was unable to be at the Spring meeting this year to receive the medal in person, but look out for her interview that will soon appear on the Node.
After a PhD in Paris on the molecular mechanisms of mRNA processing in phage, Bénédicte Sanson switched to Drosophila developmental genetics for a postdoc in Cambridge at the MRC-LMB. During her four-year postdoc with Jean-Paul Vincent (1994-1998), she investigated key aspects of Wingless signalling (the homologue of vertebrate Wnt-1) in development. Through this work, she became aware that the mechanisms underlying cell sorting at compartmental boundaries remained elusive. This fostered a long-standing interest in morphogenesis, which became the focus of her independent research group when awarded a Wellcome Trust Career Development Award in 1998, hosted in the Department of Genetics, Cambridge. Since then, Bénédicte has built up an internationally recognized research group, obtaining a Lectureship in 2009, then a Readership in 2018, in the Department of Physiology, Development and Neuroscience. In 2011 and then in 2017, she was awarded a Wellcome Trust Investigator Award to work on the mechanisms of cell sorting and collective cell movement in vivo.
Bénédicte has made key contributions to the field of developmental signaling, including demonstrating that the adhesion and signaling activities of Armadillo (the homologue of vertebrate Beta-catenin) are separable (Sanson et al., 1996) and elucidating novel signaling regulations at the parasegmental organizer in Drosophila embryos (Desbordes and Sanson, 2003; Sanson, 2001; Sanson et al., 1999). More recently, the work of her group has focused on understanding the fundamental processes driving tissue morphogenesis during development. Their work on tissue-scale forces showed that an extrinsic axial force extends the main body axis in Drosophila embryos, acting in parallel to actomyosin-dependent polarized cell intercalations (Butler et al., 2009). Next, they identified the source of this extrinsic force as caused by the invagination of the endoderm at the posterior of the embryo (Lye et al., 2015). Their work on cell sorting demonstrated that actomyosin-based mechanical “barriers” stop cells from invading adjacent compartments, pioneering CALI on GFP in Drosophila embryos to inactivate Myosin II subcellularly (Monier et al., 2010). They further showed that actomyosin-based barriers also order cells during axis extension (Tetley et al., 2016). Recently, the work of her group has shed light onto how actomyosin-driven tension can orientate cell divisions at compartmental boundaries (Scarpa et al., 2018). They also investigated how epithelial folding and actomyosin-enrichment are coupled downstream of Wingless signaling at boundaries (Urbano et al., 2018).
Underlying all of this work is a clear understanding that morphogenesis is dependent on both genetic and physical inputs. As a consequence, Bénédicte’s group often pioneers new methodologies to follow developmental processes quantitatively, and at multiple scales. Their approaches include computational methods to automatically track cell behaviours in real time, for thousands of cells; light sheet imaging (SPIM) to analyse morphogenetic events at the scale of the whole embryo; and laser cuts to probe and manipulate tissue tension. By combining such imaging and computational techniques, the lab continues to investigate how cell intrinsic and extrinsic forces integrate to shape developing tissues. Recently, Bénédicte’s group started developing computational models in collaboration with physicists and mathematicians, to explore the more mechanical aspects of morphogenesis.
In addition to her research contributions, Bénédicte has taught in a range of molecular and developmental genetics courses. Since her appointment in 2009, a significant fraction of her teaching for the University of Cambridge has been for the first year course in Veterinary Anatomy, contributing to the practical element of the course, where the students dissect the different organs and tissues. Other contributions include the active support of postdoctoral careers, both through a previous appointment at the Wellcome Trust to evaluate candidates for early career fellowships, and as Postdoc Committee Chair for her Department.
Butler, L. C., Blanchard, G. B., Kabla, A. J., Lawrence, N. J., Welchman, D. P., Mahadevan, L., Adams, R. J. and Sanson, B. (2009). Cell shape changes indicate a role for extrinsic tensile forces in Drosophila germ-band extension. Nat Cell Biol 11, 859-864.
Desbordes, S. and Sanson, B. (2003). The glypican Dally-like is required for Hedgehog signalling in the embryonic epidermis of Drosophila. Development 130, 6245-6255.
Lye, C. M., Blanchard, G. B., Naylor, H. W., Muresan, L., Huisken, J., Adams, R. J. and Sanson, B. (2015). Mechanical Coupling between Endoderm Invagination and Axis Extension in Drosophila. PLoS Biol 13, e1002292.
Monier, B., Pelissier-Monier, A., Brand, A. H. and Sanson, B. (2010). An actomyosin-based barrier inhibits cell mixing at compartmental boundaries in Drosophila embryos. Nat Cell Biol 12, 60-65.
Sanson, B. (2001). Generating patterns from fields of cells. Examples from Drosophila segmentation. EMBO Rep 2, 1083-1088.
Sanson, B., Alexandre, C., Fascetti, N. and Vincent, J. P. (1999). Engrailed and hedgehog make the range of Wingless asymmetric in Drosophila embryos. Cell 98, 207-216.
Sanson, B., White, P. and Vincent, J. P. (1996). Uncoupling cadherin-based adhesion from wingless signalling in Drosophila. Nature 383, 627-630.
Scarpa, E., Finet, C., Blanchard, G. B. and Sanson, B. (2018). Actomyosin-Driven Tension at Compartmental Boundaries Orients Cell Division Independently of Cell Geometry In Vivo. Dev Cell 47, 727-740 e726.
Tetley, R. J., Blanchard, G. B., Fletcher, A. G., Adams, R. J. and Sanson, B. (2016). Unipolar distributions of junctional Myosin II identify cell stripe boundaries that drive cell intercalation throughout Drosophila axis extension. Elife 5, e12094.
Urbano, J. M., Naylor, H. W., Scarpa, E., Muresan, L. and Sanson, B. (2018). Suppression of epithelial folding at actomyosin-enriched compartment boundaries downstream of Wingless signalling in Drosophila. Development 145.
BSDB Newsletter – Spring 2019
Please find the 2019 BSDB newsletter here!
The annual newsletter of the BSDB forms an essential summary of all that has happened over the previous year, including past and upcoming society meetings (articles 5 and 6), secretary and treasurer’s reports (articles 3 and 7), incoming committee members (article 4) and 2018 award winners (articles 11-14). At last year’s Spring meeting, a few members came to me to say how much they felt developmental biology was of great importance for the teaching of biological sciences. As an initial exploration into this issue, Bethan Clark has nicely summarized the opinions of previous Gurdon summer student awardees (article 15). Our Gurdon summer student program continues to go very well, with another set of exciting research projects that were undertaken last summer. Please take the time to have a look through their reports and see what they got up to this time around (article 16).
In this year’s AGM at the Spring meeting, we on opened a discussion around the subject of Open Access publishing. This is a highly pressing issue, as the cOAlitition S group are moving forward with PlanS to be implemented by 2020. Essentially, this will mean that researchers supported by specific funders (including the ERC, major research councils and the Wellcome Trust) will be required to publish only in entirely open access journals. For more on what this will mean for non-for-profit community journals such as those of the Company of Biologists, please see articles 8 and 9. One initiative that the Company of Biologists have launched to support the wider commenting of pre-prints is the PreLights platform, read more about this in article 10.
Remember, Ito explore the BSDB newletters of the last 10 years, they are archived on our website.
Kate Storey – Waddington medal winner 2019
Kate was first introduced to the core questions of developmental biology at the University of Sussex. She then started her research career as a graduate student in Cambridge where she already showed originality of thought and direction with an independent project on the neural development of the earthworm. This interest in understanding how a simple nervous system forms was pursued further supported with a Harkness fellowship in Berkeley, California, where she investigated leech development. On returning to UK, Kate switched to studying the development of the vertebrate nervous system where, over the years, she has made a string of exciting and important discoveries. This work has gained her international recognition in the field of developmental neurobiology and it is this, together with her many contributions to the developmental biology community, that has led to her being awarded the 2019 Waddington medal from the BSDB.
Kate Storey is now the head of the Division of Cell & Developmental Biology and Chair of Neural Development, in the School of Life Sciences, at the University of Dundee in Scotland. She investigates cellular and molecular mechanisms regulating neural differentiation in chick and mouse embryos as well as in mouse and human embryonic stem cells. By combining the advantages of each of these experimental systems, Kate has been able to gain substantial insights into the fundamental and conserved processes that regulate vertebrate neurogenesis. Her work has pioneered innovative live imaging approaches for monitoring behaviour and signalling of individual cells within developing tissues. These approaches have led to discovery of a new form of cell sub-division, named apical abscission, as well as providing insights into cell signalling dynamics that underpin asymmetric cell division. Not only is this work an excellent example of what can be learnt from observing cell biology within its normal context in vivo, it also pointed to new mechanism by which signalling is regulated during differentiation. Understanding how the dynamics of neuronal specification and differentiation is controlled during early development is a continued theme in Kate’s work.
Her earlier work showed that an interplay between FGF, Wnt and Retinoic Acid signalling is a fundamental signalling switch regulating the onset of neural differentiation. More recent findings have now linked a component of this, FGF/ERK signalling, to molecular machinery directing chromatin accessibility at neural genes. A further essential aspect of this discovery is in the provision of a mechanism by which the timing of neural differentiation can be coordinated with the progressive generation of somites within the paraxial mesoderm. Such work emphasises the ways in which developmental biologists can learn from studying processes from the sub-cellular level, through to the tissue and whole embryo level. Her discoveries have led to a programme of work that highlights the very best of developmental biology and continues to be an inspiration for young researchers entering the field.
Kate is seen as a leader in the field and has been prominent in promoting developmental biology in the UK and beyond. In Scotland, as Head of the Cell and Developmental Division of the University of Dundee since 2010, she has supported developmental biologists at different times in their careers. She has co-organized many scientific meetings including the first chick community wide meeting in 2007, the 2006 BSDB Autumn meeting on signal transduction mechanisms in development and, significantly, an EMBO workshop on spinal cord development that brought the field together for the first time in Sitges (Spain) in 2014. She has organised the Joint meeting of British, Spanish and Portuguese Societies for Developmental Biology 2015; and this year she co-chaired the Academy of Medical Sciences first international meeting on Neural Development in Oxford. Kate has in addition played an important role in the development of the field over the past ten years as a director of The Company of Biologists in particular by initiating and overseeing a series of interdisciplinary workshops on cell and developmental biology.
Kate was elected to the Royal Society of Edinburgh in 2012 and awarded the MRC Suffrage Science Heirloom Award 2014. She was elected to EMBO membership in 2016 and to the Academy of Medical Sciences 2017. In addition to her scientific achievements, Kate is known for her contributions to promoting science to a wider audience world-wide through a unique collaborative project with her sister Helen, a fashion designer. In this project, key developmental processes served as inspiration for designing textiles and dresses to chronicle the emerging human embryo. The resulting exhibition “Primitive Streak” has been seen by over 3 million people. The exhibition was one of eight major achievements identified in The Wellcome Trust’s celebration of its first 75 years, being one of the best examples of The Trust’s contribution to science communication.
Kasioulis I., Das, R.M., and Storey, K.G. (2017) Inter-dependent apical microtubule and actin dynamics orchestrate centrosome retention and neuronal delamination. eLife 2017;6:e26215.
This paper uncovers novel cytoskeletal architecture that characterises apical neuroepithelial cells. The study demonstrates how this is generated and shows that it is required for neuronal delamination.
Das, R.M. and Storey, K.G. (2014) Apical abscission alters cell polarity and dismantles the primary cilium during neurogenesis. Science 343, 200-204
This work identifies a new form of cell sub-division, apical abscission, which takes place as neurons are born and detach from the ventricular surface. This is mediated by downregulation of N-cadherin and actino-myosin contraction and involves loss of apical membrane and regulated dismantling of the primary cilium. Apical abscission may represent a new mechanism for regulating cell signaling during differentiation: loss of ciliary membrane possessing the hallmarks of active Shh signaling suggests that apical abscission curtails signaling through this pathway.
Patel, N.S., Rhinn, M., Semprich, C I., Halley, P.A., Dollé P., Bickmore, W.A., and Storey, K.G. (2013) FGF signalling regulates chromatin organisation during neural differentiation via mechanisms that can be uncoupled from transcription PLoS Genet. 2013, 9:e1003614
This paper shows that FGF signalling promotes chromatin compaction at neural genes in the mouse embryo and that this regulation of chromatin accessibility can be uncoupled from mechanisms that direct transcription.
Das, R.M. and Storey, K.G. (2012) Mitotic spindle orientation can direct cell fate and bias Notch activity in chick neural tube. EMBO Reports 13(5): 448-54
This paper shows that apico-basally-orientated cell-division generates an apical daughter that becomes a neuron and a basal daughter that elevates Notch activity and divides again in the chick neural tube. The work links asymmetric division to Notch signalling dynamics and identifies a new neuronal differentiation step in which apical cells commencing neuronal differentiation rapidly lose apical complex proteins.
Olivera-Martinez I, Harada H, Halley PA, Storey KG (2012) Loss of FGF-Dependent Mesoderm Identity and Rise of Endogenous Retinoid Signalling Determine Cessation of Body Axis Elongation. PLoS Biol 10(10): e1001415 doi:10.1371/journal.pbio.1001415
This paper provides a mechanism for cessation of body axis elongation in the chick. It reveals a sudden and discrete loss of FGF-dependent mesoderm identity gene brachyury in the late tailbud and shows that this is due to breakdown of oppositional signalling between FGF and retinoid pathways.
Delfino-Machín, M., Lunn, J.S., Breitkreuz, D.N., Akai, J. and Storey, K.G. (2005) Specification and maintenance of the spinal cord stem zone. Development 132, 4273-83.
Characterizes the stem zone (now known as the Caudal Lateral Epiblast, CLE) of the chick embryo and shows that cells here express both neural and mesodermal genes. The work demonstrates the requirement (but not sufficiency) for FGF signalling for the induction and maintenance of stem zone (CLE) and the differential regulation of Hox genes in the elongating body axis.
Diez del Corral, R., Olivera-Martinez, I., Goriely, A., Gale, E., Maden, M., and Storey, K (2003) Opposing FGF and Retinoid pathways control ventral neural patterning, neuronal differentiation and segmentation during body axis extension. Neuron 40, 65-79.
This work describes the discovery of an oppositional signalling switch between FGF and retinoic acid that controls differentiation onset in the body axis. FGF represses differentiation, while retinoic acid attenuates Fgf8 in neuroepithelium and paraxial mesoderm, where it controls somite size, and is further required for neuronal differentiation and expression of key ventral patterning genes.
David Munro – Beddington Medal Winner 2019
Jim Smith introduced the Beddington medal with heartfelt memories of Rosa Beddington and her time at the NIMR. Please read more of his thoughts here.
Some complicated selfies were taken as the medal was passed over before David went on to present the work that has deserved him this award. In the words of his PhD supervisor:
“The really impressive thing about David’s work is that he did not come to my lab to fit in with an existing line of research but created one of his own”. Jamie Davies, University of Edinburgh.
David received his undergraduate degree in Sport and Exercise Science at the University of Stirling (2010-2014). With this, he achieved a first-class honours degree and the prize for the best overall performance throughout a physiology related degree (British Physiological Society Undergraduate Prize). His dissertation project investigated associations between ADRB2 mutations (an adrenaline receptor gene in humans) and athlete status/athletic ability measurements. Subsequently, he was awarded a University of Stirling Head of School Summer Bursary Award to remain in Stirling during the summer of 2014 and investigate the relationship between transcribed ultra-conserved regions of RNA (T-UCRs) and the development of diet-induced insulin resistance in humans (Summer 2014). He then moved to the University of Edinburgh for his MSc by Research in Biomedical Sciences (2014-2015). Again, he received a distinction and was awarded the Class Prize for best student. During this time, he studied the physiology of S-acylation the regulation of skeletal muscle energy expenditure by an obesity-associated phospholipase as part of two research placements.
David has been awarded the Beddington medal for his exceptional work performed during his 3-year MRC-funded PhD at the University of Edinburgh with Prof Jamie Davies and Dr Peter Hohenstein (2015-2018): The thesis is titled ‘Mechanisms of kidney vascularisation and the roles of macrophages in renal organogenesis’. During his PhD, he gave several oral and poster presentations at national and international conferences, supervised students (including a Gurdon Summer Studentship Awardee), established numerous international collaborations, was awarded travel grants (including a BSDB Conference Grant), and reviewed manuscripts for leading journals (including Cell Reports, Angiogenesis, and Scientific Reports). He is now a post-doctoral fellow at the UK Dementia Research Institute (University of Edinburgh; 2019- present), continuing research in macrophage biology under the supervision of Prof Josef Priller. His current focus in on brain macrophages (microglia) in development, neurodegeneration, and aging.
Kidneys are specialised organs that clean the blood, removing waste while retaining what is useful. This requires a complex vasculature, and its formation as a foetus develops is poorly understood. I started my PhD research by using advanced microscopy techniques to visualise how blood vessels form in three-dimensions in the mouse kidney. In doing so, I identified when and from where the first blood vessels enter the kidney, and how blood vessels pattern at the edge of the kidney throughout development.
Blood vessels can form through angiogenesis (branching of new vessels from pre-existing ones) and/or vasculogenesis (assembly of new vessels from the coalescence of endothelial precursor cells). It has long been thought that a combination of both processes occurs during kidney vascularisation; however, my thesis work indicates that this concept may not be correct. My data instead suggest that kidney vascularization relies on growth and remodelling of pre-existing vessels (angiogenesis) and does not depend on vasculogenesis at any point (Publications 1 and 5 in CV). When assessing the entire 3D vascular tree of the kidney, isolated endothelial cells were never observed at any developmental age. Instead, all vessels, including the newly forming ones, were connected to pre-existing vessels that could be traced to the major circulatory vessels.
I then focused on the blood vessels at the edge of the kidney, which I found to consistently and accurately pattern around a special collection of cells – the cap mesenchyme. The cap mesenchyme contains cells that eventually become the cleaning tubes of the kidney, the nephrons. This cell population undergoes rounds of splitting at the kidney’s periphery. As this happens, I demonstrated that blood vessels migrate through the newly opened regions between the separating cap mesenchymal populations (Publication 1 in CV). This occurs in cycles throughout development and is likely to be vital for the oxygenation of the kidney’s outer region, the site where important processes such as nephron formation take place.
I determined that a signalling molecule, semaphorin-3f, and its receptor, neuropilin-2, were expressed in a pattern consistent with them having roles in this cyclical patterning of blood vessels; however, using mouse models where the genes for these molecules were deleted, I established that they were not vital for this process (Publication 2 in CV).
I next shifted my research focus towards a specialised cell type known as the macrophage (macro = big; phage = eater) in the developing kidney (Publication 3 in CV). Macrophages are immune cells best known for clearing foreign and damaged cells. These cells have vital roles during animal development, but little is known about their specific functions during kidney development.
Macrophages arrived in the mouse kidney early during its development, where they were required to clear away misplaced cells to ‘set-the-stage’ for early kidney development (Publication 6 in CV, under review). Throughout later development, most macrophages wrapped around blood vessels and I demonstrated their ability to eat endothelial cells (which usually line the blood vessels) and red blood cells (which are carried within them) within the kidney. I also established that kidney macrophages produced many molecules linked to blood vessel development, and so I examined the consequences of macrophage-loss on blood vessel formation. Blood vessels normally form continuous networks in the kidney; however, when macrophages were depleted (by blocking a macrophage-survival signalling pathway), connections between renal blood vessels were reduced (Publication 6 in CV).
- Munro DAD, Hohenstein P, Davies JA. 2017. Cycles of vascular plexus formation within the nephrogenic zone of the developing kidney. Scientific Reports. 7: 3273.
- Munro DAD, Hohenstein P, Coate TM, Davies JA. 2017. Refuting the hypothesis that semaphorin-3f/neuropilin-2 guide endothelial patterning around the cap mesenchyme in the developing kidney. Developmental Dynamics. 246:1047-1056.
- Munro DAD, Hughes J. 2017. The Origins and Functions of Tissue-Resident Macrophages in Kidney Development. Frontiers in Physiology. 8:837. (Review)
- Mills CG, Lawrence ML, Munro DAD, El-Hendawi M, Mullins JJ, Davies JA. 2017. Asymmetric BMP4 signalling improves the realism of kidney organoids. Scientific Reports. 7:14824.
- Munro DAD, Davies JA. 2018. Vascularizing the kidney in the embryo and organoid: questioning assumptions about renal vasculogenesis. Journal of the American Society of Nephrology. (Perspectives article).
- Munro DAD, et al. Macrophages restrict the nephrogenic field and promote endothelial connections during kidney development. eLife 2019;8:e43271 DOI: 10.7554/eLife.43271