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Rôle du récepteur BAI3 dans le développement neuronal - Études in vitro et in vivo -

Abstract : Dendritogenesis and spinogenesis constitute key steps of neuronal development. They involve many proteins that play an essential role in the reorganization of the actin cytoskeleton through RhoGTPases. Defects in these processes can lead to neurodevelopmental disorders such as autism or schizophrenia. BAI receptors belong to the family of adhesion-GPCRs and have been identified in biochemical preparations of post-synaptic densities. BAI1 modulates the RhoGTPase Rac1 via its interaction with the protein ELMO1 in non-neuronal cells. C1q-like secreted proteins were recently identified as ligands for the BAI3 receptor in vitro and this interaction might regulate synaptogenesis. We thus hypothesized that BAI3 could regulate neuronal development, especially dendritogenesis and spinogenesis, via its interaction with ELMO1. Our work showed that BAI3 localizes in developing dendrites, and in mature neurons in dendritic spines. In vitro, morphometric studies have shown its role in the growth and complexity of the dendritic tree. In vivo, BAI3 is involved in the morphogenesis of cerebellar Purkinje cells and in the development of their excitatory innervation. These effects appear to depend in part on BAI3's interaction with ELMO1. BAI3 modulates cell spreading, suggesting its involvement in the regulation of RhoGTPases. Altogether, our results highlight a new role of BAI receptors as regulators of dendritogenesis and synapse formation partly via the signaling pathway ELMO1/Rac1. Given the potential link between BAI3 and some symptoms of schizophrenia, our results identify the BAI receptors as new players in neuronal morphogenesis and offer new perspectives in the study of neurodevelopmental disorders.
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https://tel.archives-ouvertes.fr/tel-00865692
Contributor : Vanessa Lanoue <>
Submitted on : Tuesday, September 24, 2013 - 10:10:05 PM
Last modification on : Wednesday, October 14, 2020 - 4:05:36 AM
Long-term archiving on: : Wednesday, December 25, 2013 - 4:42:13 AM

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  • HAL Id : tel-00865692, version 1

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Vanessa Lanoue. Rôle du récepteur BAI3 dans le développement neuronal - Études in vitro et in vivo -. Neurosciences. Université Pierre et Marie Curie - Paris VI, 2012. Français. ⟨tel-00865692⟩

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