Etude de l'influence de la topographie du microenvironnement sur la migration des interneurones corticaux par l'utilisation de substrats microstructurés

Abstract : In the developing brain, cortical interneurons undergo a long distance migration to reach the cortex where they integrate into cortical networks and regulate their activity in the adult. Different chemical factors have been involved in the guidance of these cells, but the influence of the physical parameters of the environment in which they navigate remains unclear. It has been shown that topographical cues are able to influence and guide the migration of several cell types, a process called contact guidance. This work therefore aimed at testing and understanding the influence of the topography of the environment in the migration of cortical interneurons. By using an experimental system of microstructured substrates, we demonstrated for the first time the existence of contact guidance for these cells. By testing two types of micron-sized pillars, we showed that a change in the shape of the structures could greatly impact cell orientation, morphology, cytoskeleton organization and dynamic behavior. In particular, most interneurons migrating in between square pillars adopt an elongated, unbranched morphology associated with a slow and directed movement, whereas the majority of cells among round pillars exhibit a short and branched morphology associated with a dynamic but wandering movement. Overall, we show that micron-sized topography provides global spatial constraints promoting the establishment of different morphological and migratory states in vitro, highlighting the potential importance of these types of cues in vivo.
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Claire Leclech. Etude de l'influence de la topographie du microenvironnement sur la migration des interneurones corticaux par l'utilisation de substrats microstructurés. Biophysique. Sorbonne Université, 2018. Français. ⟨NNT : 2018SORUS245⟩. ⟨tel-02387369⟩

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