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• W2517596995 abstract "Event Abstract Back to Event Influence of topography on cortical interneuron migration in microstructured environments Claire Leclech1, Rachel Gibel-Russo1, Catherine Villard2 and Christine Métin1* 1 Institut du Fer à Moulin INSERM U839, France 2 UMR 168 « Physicochimie Curie » CNRS/UPMC/Institut Curie, France In the adult brain, the cerebral cortex contains pyramidal neurons which are output neurons and interneurons, mostly inhibitory. Convergent evidence shows that interneurons are essential for computation by cortical circuits. During brain development, interneurons migrate a long distance to reach the cerebral cortex. Their correct positioning is crucial for the normal control of cortical activity. In particular, abnormal development or function of interneurons is now considered as a major factor in psychiatric diseases such as schizophrenia or epilepsy. Migrating interneurons are highly polarized cells with a long leading process at the cell front that explores the environment and adheres to the substrate. As previously described for growing axons, the migration of cortical interneurons is influenced by chemotactic molecules distributed as gradients in the extracellular space and by adhesive molecules. These cues are transduced in the growth cone and influence cytoskeleton dynamics. Interestingly, physical cues such as topography or substrate stiffness have also been shown to guide axonal growth, a process that resembles leading process navigation. However, the contribution of physical cues in interneuron migration remains largely unknown. To further investigate the influence of topography on interneuron migration, we developed a migration assay using microfabrication tools, in which migrating interneurons from mouse embryonic brains are cultured on microstructured surfaces of PDMS coated with a mix of adhesion molecules. We observed that migrating interneurons are indeed sensitive to topography and respond differently to isotropic (forest of pillars) or anisotropic (grooves) topography. Interestingly, we observed that the leading process of interneurons migrating in isotropic topography was highly sensitive to the shape and spacing of structures. In particular, leading processes of interneurons migrating among square pillars presented a stereotyped alignment which was rarely observed on round pillars. Cytoskeleton organization and dynamics differed on these two substrates, showing that topographical cues in the cellular environment can greatly influence the morphology and dynamic properties of the leading process. By using these biophysical approach, we hope to shed light on the influence of a new class of guidance cues –physical guidance- on migrating neurons. In the highly controlled environment of microstructured surfaces, we should be able to precisely characterize the cellular defects altering the migration of interneurons with mutations involved in human cortical malformations and neurodevelopmental psychiatric disorders. Résumé en Français: Les défauts de positionnement des interneurones dans le cortex cérébral sont à l’origine de nombreuses maladies neurodéveloppementales et neuropsychiatriques. La mise en place de ces cellules a lieu pendant le développement embryonnaire, à la suite d’une très longue migration qui utilise les molécules présentes dans l'environnement comme signaux de guidage. La contribution des paramètres physiques de l’environnement reste méconnue. Pour étudier l’influence de ces paramètres sur la migration des interneurones, nous avons développé par microfabrication des substrats présentant un micro-relief. Nous montrons que les interneurones, spécialement leur prolongement migrateur, sont très sensibles à la géométrie du relief. Samenvatting in het Nederlands: Foutieve instelling van interneuronen in de hersenschors liggen aan de basis van heel wat neuro ontwikkelings- en neuropsychiatrische ziektes. Het plaatsen van de cellen gebeurt tijdens de embryonale ontwikkeling, op basis van een zeer lange migratie die gebruik maakt van de moleculen aanwezig in de omgeving als bakens. De bijdrage van fysieke parameters van de omgeving blijft miskend. Om de invloed van deze parameters op de migratie van neuronen te bestuderen, hebben we door microfabricatie substraten ontwikkeld met een micro reliëf. We tonen aan dat de interneuronen, en in het bijzonder het verderzetten van hun migratie, zeer afhankelijk zijn van de geometrie van het reliëf. Acknowledgements We acknowledge the french MESNER for supporting CL with a thesis fellowship and INSERM and Agence Nationale pour la Recherche for research funding (grant Migracil to CM). Microfabrication was performed on the Plateau Technologique of Institut Pierre-Gilles de Gennes. Live cell imaging was performed at the plateforme d'imagerie de l'Institut du Fer à Moulin. References [1] Christine Métin, Richard B. Vallee, Pasko Rakic, and Pradeep G. Bhide (2008) Modes and Mishaps of Neuronal Migration in the Mammalian Brain. The Journal of Neuroscience, 28(46): 11746-11752 [2] Camilla Luccardini, Laetitia Hennekinne, Lucie Viou, Mitsutoshi Yanagida, Fujio Murakami, Nicoletta Kessaris, Xufei Ma, Robert S. Adelstein, René-Marc Mège, and Christine Métin (2013) N-Cadherin Sustains Motility and Polarity of Future Cortical Interneurons during Tangential Migration. The Journal of Neuroscience, 33(46):18149 –18160 [3] Camillar Luccardini, Claire Leclech, Lucie Viou, Jean-Paul Rio, Christine Métin (2015) Cortical interneurons migrating on a pure substrate of N-cadherin exhibit fast synchronous centrosomal and nuclear movements and reduced ciliogenesis. Front Cell Neurosci. 2015; 9: 286. [4] Diane Hoffman-Kim, Jennifer A. Mitchel and Ravi V. Bellamkonda (2010) Topography, Cell Response, and Nerve Regeneration. Annu. Rev. Biomed. Eng. 12:203–31 Keywords: Cortical development, cortical interneurons, Migration, Cytoskeleton, topography, Physical guidance, Microfabrication techniques, Cell Culture Techniques Conference: 6th Belgian Brain Congress, MONS, Belgium, 8 Oct - 8 Oct, 2016. Presentation Type: Poster Presentation Topic: Brain and brain diseases: between heredity and environment Citation: Leclech C, Gibel-Russo R, Villard C and Métin C (2016). Influence of topography on cortical interneuron migration in microstructured environments. Conference Abstract: 6th Belgian Brain Congress. doi: 10.3389/conf.fnagi.2016.03.00062 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 12 Jul 2016; Published Online: 13 Jul 2016. * Correspondence: PhD. Christine Métin, Institut du Fer à Moulin INSERM U839, Paris, 75005, France, christine.metin@inserm.fr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Claire Leclech Rachel Gibel-Russo Catherine Villard Christine Métin Google Claire Leclech Rachel Gibel-Russo Catherine Villard Christine Métin Google Scholar Claire Leclech Rachel Gibel-Russo Catherine Villard Christine Métin PubMed Claire Leclech Rachel Gibel-Russo Catherine Villard Christine Métin Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page." @default.
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