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Master de Sciences et Technologies Mention Biologie Intégrative et Physiologie Spécialité : Neurosciences Responsable : Professeur Régis LAMBERT Proposition de Stage M2 S4 NEUROSCIENCES Année Universitaire 2016-2017 1. Equipe d’Accueil de Master (EAM) : Intitulé et numéro de l’Unité : Institut Du Cerveau et de la Moelle (ICM / Inserm U1127, UPMC UMR_S1127, CNRS UMR7225 Nom du Responsable de l’Unité : Brice Alexis Nom du Responsable de l’Équipe : Fontaine Bertrand Intitulé de l’équipe d’accueil : Neurogénétique et Physiologie Adresse : Hôpital de la Pitié-Salpêtrière - 47, boulevard de l'Hôpital 75013 Paris Nom du responsable de l’encadrement : Strochlic Laure Tél. : 0157274404 Fax. : E-mail : [email protected] 2. Titre du sujet : Etude du rôle de la voie de signalisation MuSK/Wnt à la Jonction Neuromusculaire / Study of Wnt signaling mechanisms at the Neuromuscular Junction. 3. Description du sujet : Neuromuscular junction (NMJ) development requires a temporally fine-tuned balance of distinct signaling activities initiated from muscle or motoneuronal-secreted molecules. Any disruption of these signaling activities drastically affects NMJ formation and maintenance and may lead to neuromuscular diseases. Therefore, it remains critical to understand the molecular and cellular mechanisms orchestrating the formation and maintenance of the neuromuscular connectivity during embryonic development and in adulthood in order to develop therapies based on new molecular targets. How do signals arising from the muscle and the nerve orchestrate the formation and maintenance of the neuromuscular connectivity? How does the disruption of the brain and skeletal muscle communication cause neuromuscular disorders? These are key questions regarding neuromuscular development and maintenance remaining to be investigated. Recent data from the literature emphasize the role of Wnts molecules in NMJ formation and maintenance. However, the cooperative role of Wnts and the signaling pathway involved in the differentiation of pre and postsynaptic compartments of the NMJ remain largely unknown. Our team has recently generated a transgenic mouse bearing the deletion of the Wnt binding domain (CRD) of the tyrosine kinase receptor called MuSK, a central player in NMJ formation. Embryonic MuSK CRD deficiency alters downstream activation of canonical Wnt signaling, causes profound defects of NMJ formation and leads in adult to a congenital myasthenic-like phenotype (Messéant et al., 2015). The goal of this project is to provide both fundamental and preclinical insights on the key regulators of the neuromuscular synapse in vivo, investigating the Wnt signals and associated signaling pathways in the muscle and the motoneuron that orchestrate the formation and maintenance of the neuromuscular connectivity. Master de Sciences et Technologies Mention Biologie Intégrative et Physiologie Spécialité : Neurosciences Responsable : Professeur Régis LAMBERT To realize this project, the student will use biochemistry and cell biology approaches both in vitro (muscle cell culture) and in vivo (transgenic mice lines). He will be supervised by a chargé de recherche INSERM (CR1), holding an HDR.