Chairs
Dr Gislene Pereira, University of Heidelberg, Germany
Dr Gislene Pereira, University of Heidelberg, Germany
Gislene Pereira is an independent group leader at the Centre for Organismal Studies and Cancer Research Centre at the University of Heidelberg, Germany. She has trained at the University of São Paulo, Brazil (BSc in Pharmacy and MSc in Biochemistry), Ludwig-Maximilliam University, Munich, Germany (PhD in Biochemistry) and at the Beatson and Paterson Institutes for Cancer Research, UK (postdoctoral fellow). Before moving to Heidelberg, she was a Lecturer at the School of Biological Sciences, University of Manchester, UK. Her research interests cover centrosome-driven cell signalling, cilia biogenesis and the control of cell polarity/asymmetric cell division. Her work pioneered the elucidation of a spindle-related mitotic checkpoint and defined the mode of centrosome inheritance in asymmetrically dividing yeast cells, which later proved to be conserved in stem cells of higher eukaryotes. Her laboratory also identified novel regulators of cell polarity establishment and important molecular players that regulate cilia biogenesis at the centrosome.
13:30-13:55
Integrating daughter cell self-renewal and fate-choice during retinogenesis
Dr Lucia Poggi, University of Heidelberg, Germany
Abstract
One focus of regenerative medicine is to efficiently and safely replace retinal ganglion cells (RGCs), the output neurons of the retina, which are lost upon glaucoma and optic neuropathies leading to irreversible blindness. To this end, a tightly controlled expansion of the source cell (stem, progenitor or even differentiated neuronal cells) as well as its efficient and safe reprogramming into functional RGCs is needed. Achieving this requires that we understand the complex crosstalk of cell fate determinants, chromatin regulators and self-renewal factors that are at work during the normal genesis of RGCs in vivo. The bHLH transcription factor Ath5 (Atoh7) plays a crucial role in instructing RGC fate acquisition of retinal progenitor cells as well as induced pluripotent stem cells and Müller glia. Expression of ath5, however, is not decisive for RGC commitment and cells escape the RGC fate while progressing through self-renewal states. Poggi is interested in disentangling the integrated molecular interactions, from daughter cell inheritance to transcriptional regulation, which allow ath5-expressing progenitors to elude the RGC differentiation pathway upon asymmetric cell division. To understand this, Poggi began with interrogating gene regulatory networks controlled by Ath5, and to examine them in the physiological cellular context of the three-dimensionally patterned retinal tissue of the developing zebrafish embryo. Here Poggi provides insights suggesting how reciprocal feedbacks between Ath5 and factors influencing multipotency and self-renewal might intersect during asymmetric cell division, to restrict the RGC fate choice of retinal progenitor cells.
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Dr Lucia Poggi, University of Heidelberg, Germany
Dr Lucia Poggi, University of Heidelberg, Germany
Lucia Poggi received her MSc and PhD in Molecular Cell Biology from the University of Pisa. Following completion of an internship at EMBL Heidelberg, she moved to the University of Cambridge to carry out her postdoctoral work. During this time, Lucia developed time-lapse imaging methods in the retina of the zebrafish embryo to study lineage and modes of division of retinal stem cells in their native environment. After being awarded a DFG Research Grant for Principal Investigator, Lucia was appointed Independent Junior Group Leader in the Centre for Organismal Studies at University of Heidelberg and member of the Interdisciplinary Centre for Neuroscience. She recently joined the Department of Ophthalmology - David J Apple Laboratory at the University of Heidelberg. Her current research interests focus on understanding the mechanisms of asymmetric cell division and daughter cell identity acquisition during eye development and regeneration.
14:00-14:25
Asymmetric cell division in Ciona notochord tapering
Dr Michael Veeman, Kansas State University, USA
Abstract
Tapering body parts are common in nature, but little is known about the developmental mechanisms by which taper arises. The simple 40 cell notochord of the invertebrate chordate Ciona forms a tapered rod, and the Veeman group are using it as a model for dissecting the mechanisms of tapering. Much of the taper reflects the cells at the front and back of the notochord being progressively smaller in volume than cells in the middle. Veeman used a genetic fate mapping strategy based on mosaic expression of an electroporated transgene to show that asymmetric division is the major driver of these anterior to posterior cell volume differences. Cells in the anterior of the notochord primordium divide to give smaller anterior daughters, and cells in the posterior of the primordium divide to give smaller posterior daughters. The volume asymmetries seen are modest compared with many cases of asymmetric division, but two consecutive rounds of division with complex patterns of asymmetry lead to important changes in cell size and ultimately help control the shape of an entire chordate organ. Veeman is currently investigating the cellular and molecular mechanisms driving these novel asymmetric divisions. The mitotic spindle becomes robustly oriented along the AP axis in these cells, but it is not clear if it is being displaced. The group are working to test an alternate hypothesis that some of these asymmetric divisions might involve a centred spindle in the context of an asymmetrically shaped cell.
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Dr Michael Veeman, Kansas State University, USA
Dr Michael Veeman, Kansas State University, USA
Michael Veeman’s group uses quantitative imaging and functional genomics approaches in the simple chordate Ciona to study how genomes encode spatial information. Ciona has a stereotyped chordate embryonic body plan but in an unusually small, simple embryo well suited to quantitative imaging. One project in the laboratory seeks to understand the functions and mechanisms of asymmetric division in controlling the tapered shape of the larval tail. Another project works towards a systems-level understanding of Ciona notochord morphogenesis. Michael trained at the University of Alberta (BSc), the University of Washington (PhD with Randy Moon) and the University of California Santa Barbara (postdoc with Bill Smith). He has been an Assistant Professor at Kansas State University since 2011.
15:00-15:25
Live imaging reveals new aspects of zebrafish neurogenesis
Dr Paula Alexandre, University College London, UK
Abstract
During development of central nervous system (CNS) neural progenitors must be able to self-renew while producing neurons by undergoing series of asymmetric divisions. During early stages of zebrafish embryonic development, differentiated neurons appear regularly spaced along the anterior posterior axis of the spinal cord. This suggests that a mechanism that spaces neural progenitors’ asymmetric divisions or differentiating neurons must exist in this region. To determine the cellular and molecular mechanisms that can regulate neuronal patterning in the neural tube, Alexandre used live-imaging in zebrafish embryo to monitor neural progenitors’ divisions and neurons differentiating in vivo. Alexandre discovered that neuronal committed progenitors transiently elongate two long basal processes along the antero-posterior axis of the neural tube. The Alexandre group has evidence that signals delivered by these long processes may prevent neighbours from differentiating. This is the first cellular behaviour found in a vertebrate system that can regulate neuronal patterning in the neural tube.
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Dr Paula Alexandre, University College London, UK
Dr Paula Alexandre, University College London, UK
Paula Alexandre studied Biochemistry at “Faculdade de Ciencias”, University of Lisbon. Paula obtained her PhD in 2005, working in Dr Marion Wassef’s laboratory at "Ecole Normale Superieure" in Paris and studying the mid hindbrain signals that orchestrate cell movements and refine patterning of the midbrain. During this period she has been awarded several fellowships from "Fundacao para a Ciencia e Tecnologia" (Portugal), "Fondation des Treilles" and "Fondation pour la Recherche Médicale" (France). In 2006, Paula Alexandre joined Professor Jon Clarke’s laboratory at University College London (UCL) as a post doc and later moved with the group to King’s College London (KCL). During this period she developed long-term imaging in a zebrafish embryo to study the mechanisms that regulate progenitors asymmetric divisions during zebrafish neurogenesis and has been awarded an EMBO and IEF Marie Curie’s fellowships. In 2013, funded by the Dorothy Hodgkin Fellowship from the Royal Society, Paula Alexandre joined the UCL Institute of Child Health as a principal investigator where she continues studying the mechanisms that regulate neurogenesis.
15:30-15:55
Proliferation control in Drosophila neural stem cells
Dr Catarina Homem, CEDOC, Universidade Nova de Lisboa, Portugal
Abstract
Stem cells are highly abundant during early development but become rare in most adult organs. Stem cell numbers must then be tightly regulated during development, but the molecular mechanisms causing stem cells to exit proliferation at a specific time are unclear. To address the mechanisms triggering stem cell exit during development Homem used Drosophila neural stem cells, the neuroblasts. Neuroblasts undergo size and fate asymmetric divisions to self-renew and generate more differentiated cells. Neuroblasts proliferate during development but all exit cell cycle and disappear before adulthood. Homem’s data show that changes in energy metabolism induced by the steroid hormone Ecdysone together with transcription regulator Mediator initiate an irreversible cascade of events leading to neuroblast differentiation. An increase in the levels of oxidative phosphorylation in neuroblasts leads to uncoupling between cell cycle from cell growth. This results in progressive reduction in neuroblast cell size and ultimately in terminal differentiation. Homem’s findings show that neuroblast size control can be modified by systemic hormonal signalling and reveal a unique connection between metabolism and proliferation in stem cells.
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Dr Catarina Homem, CEDOC, Universidade Nova de Lisboa, Portugal
Dr Catarina Homem, CEDOC, Universidade Nova de Lisboa, Portugal
Catarina Homem is a Principal Investigator at the Center for Chronic Diseases (CEDOC) at the University Nova of Lisbon, Portugal. Her main research interests are on how stem cell fate and proliferation are regulated during animal development. Her laboratory focuses on the mechanisms of cell fate regulation in neuroblasts, Drosophila's asymmetrically dividing neural stem cells.
Catarina Homem did her PhD under the supervision of Dr Mark Peifer at UNC, Chapel Hill, USA where she researched how the actin cytoskeleton dynamically regulates Drosophila morphogenesis. For her postdoctoral work she joined the laboratory of Dr Juergen Knoblich at IMBA in Vienna, Austria where she started exploring the role of metabolism in the regulation of stem cells.
16:00-16:25
Centrosome asymmetry and Notch signalling in spinal cord neural progenitors
Dr Xavier Morin, Institut de Biologie de l'Ecole Normale Superieure, France
Abstract
Unequal maturation of centrosomes has been associated with differential fate choices in several models of asymmetric cell division, including vertebrate neural stem cells. Nevertheless, signalling molecules taking advantage of the intrinsic centrosome asymmetry to instruct binary fate choices in sister cells have yet to be identified. Morin’s group found that the mono-ubiquitin ligase Mindbomb1 (Mib1), a regulator of the Notch pathway, localizes to centriolar satellites associated with the daughter centrosome of chick spinal cord progenitors. Using live imaging and fate tracking in the neural tube, we show that during asymmetric divisions, the centrosome carrying this pool of Mib1 is inherited by the prospective neuron. However, in symmetric divisions, a second pool of Mib1 associated with the Golgi apparatus in interphase is released during mitosis, aggregates on the free centrosome, and compensates for the initial Mib1 centrosomal asymmetry. Remarkably, as development of the neural tube proceeds, Mib1 is progressively lost from the Golgi apparatus, correlating with the reduction in symmetric proliferative divisions. Thus, the Golgi apparatus may represent a storage compartment compensating for the centrosome asymmetry of Mib1 in proliferative divisions. As neurogenesis progresses, this compensatory mechanism fades out and neurogenic divisions become predominant. Finally, Morin shows that preventing Mib1 centrosomal association in dividing cells hinders Notch signalling and delays neuronal differentiation in daughter cells. Thus, Morin establishes for the first time a link between centrosome asymmetry and Notch signalling, and propose that changes in the subcellular localization of Mib1 in neural progenitors are instrumental for the progression of neurogenesis.
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Dr Xavier Morin, Institut de Biologie de l'Ecole Normale Superieure, France
Dr Xavier Morin, Institut de Biologie de l'Ecole Normale Superieure, France
After graduating from the Ecole Normale Supérieure in Paris in 1995, Xavier Morin obtained a PhD at the Developmental Biology Institute in Marseilles, deciphering the role of transcription factors in mouse autonomous nervous system development. During his postdoc with William Chia at the IMCB Singapore and King’s College London, his contribution to the identification of a key regulator of mitotic spindle orientation and fate decisions in Drosophila sparked his interest in asymmetric division of neural progenitors. Upon returning to France as a junior investigator at the CNRS in 2003, he studied whether concepts discovered in the fly apply to the vertebrate developing nervous system. In 2010, he started the Cell Division and Neurogenesis laboratory at the Biology Institute at the Ecole Normale Supérieure, using the chick embryonic spinal cord to investigate how events occurring during neural progenitors’ division have an impact on the fate of their progeny.
16:30-16:55
How are mechanical factors controlled during brain formation?
Dr Yoichi Kosodo, Korea Brain Research Institute, South Korea
Abstract
During brain development, neural stem cells define specific niches within different cortical layers to control their cellular environment. Generally, communication to other cells or surrounding matrix by biochemical signalling pathways such as protein-protein interactions or soluble factors have been well studied. Much less studied, however, is how physical properties of the niche can influence behaviour, growth, and differentiation of cells. Among physical properties, stiffness of the matrix has been shown to have direct effects on fate determination in certain stem cell types in vitro. While some studies indicate that stiffness may influence the fate of cultured neural stem cells by unknown mechanisms, little evidence exists on whether this principle holds true during the physiological development of the mammalian brain in vivo. Here, Kosodo has characterized tissue stiffness of the developing mouse brain cortex by using atomic force microscopy to seek a link to the cell fate determination of neural cells via mechanosignalling pathways, and found specific spatiotemporal shifts in stiffness during brain formation. The research aims to establish a novel concept for mammalian neurogenesis and brain development, and the outcomes will likely influence the fields of stem cell and developmental biology by clarifying unknown mechanosignalling mechanisms of somatic stem cells.
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Dr Yoichi Kosodo, Korea Brain Research Institute, South Korea
Dr Yoichi Kosodo, Korea Brain Research Institute, South Korea
Yoichi Kosodo is a Principal Investigator at the Korea Brain Research Institute (KBRI), Daegu, South Korea. His laboratory investigates mammalian neurogenesis by pursuing the concept of how tissue and cells reciprocally influence and regulate each other to form the robust architecture of our brain. To illustrate such regulatory systems of neurogenesis, the group has been constructing novel models, and examining their consistency by applying interdependent experimental approaches, such as methods of molecular cell biology, live-imaging, quantitative biology and biomaterials. The research group currently focuses on how physical factors in tissue regulates neural differentiation during brain development.