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Régulation de la stabilité du cytosquelette microtubulaire : conséquences sur la croissance de la jonction neuromusculaire chez la Drosophile

Abstract : During the development of the nervous system, several molecular mechanisms are involved in axon pathfinding and synapse formation. Once the synapses are established, they remain plastic et can undergo morphological and functional modifications depending on target size or synapse activity. The neuromuscular junction (NMJ) of Drosophila larva is a very powerful model to study such developmental synaptic plasticity. Indeed, the size of the innervated muscle increases 50 times and the NMJ grows consequently. NMJ growth involves microtubules cytoskeleton, a key element of synaptic endings. In this work, we studied the role of the kinase Shaggy in NMJ growth, and we showed that this kinase negatively controls synaptic expansion depending on a structural microtubule associated protein (MAP), Futsch. Structural MAPs are separated in two families, MAP1 (MAP1A, MAP1B, MAP1S) and MAP2/MAP4/Tau. These proteins are known to stabilize microtubules and to promote neuritic growth, in the nervous system. However, their role in late stages of synaptogenesis remain unknown. In Drosophila, only one single member of each family is encoded by the genome, Futsch (MAP1) and Tau (MAP2/MAP4/Tau). Though, the study of each family is easier in Drosophila due to lower redundancy. We studied the role of these MAPs on microtubules stability and the consequences on NMJ growth and synapse specialization. We also, studied signalling pathway members, those involved in the Wnt/Wingless pathway, known to regulates structural MAPs.
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Submitted on : Friday, December 14, 2007 - 12:47:06 PM
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Bénédicte Franco. Régulation de la stabilité du cytosquelette microtubulaire : conséquences sur la croissance de la jonction neuromusculaire chez la Drosophile. Neurosciences [q-bio.NC]. Université Montpellier I, 2007. Français. ⟨tel-00195343⟩

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