2000-2004: PhD Cell Biology and Biochemistry. University Paris VI. Laboratoire de biologie cellulaire des membranes. Institut Jacques Monod. PhD supervisor: Dr Jean Cartaud.
Identification and role of the MuSK signaling partners at the neuromuscular junction.
Fellowships: MENRT and AFM.
2004-2007: Postdoctoral position in Pr Christine Holt's laboratory at Cambridge University.
S1P: A new guidance cue for retinal growth cones.
Identification of retinal growth cone newly synthesised proteins.
Fellowships: Marie Curie European fellowship
2007-2010: Postodoctoral position in Pr Claire Legay's laboratory at the University Paris Descartes.
Fellowships: AFM, CDD Inserm jeune chercheur.
2010-2014: Inserm permanent position in Pr Claire Legay's laboratory at the University Paris Descartes.
Wnt and neuromuscular junction formation.
Grant: AFM trempoline grant
2015-2018: Inserm permanent position in Pr B. Fontaine's laboratory at the Brain and Spine Institute (ICM)
Grants: AFM, Fondation de l'avenir, SATT Lutech, AFM strategic
Synapses form in three steps including specific target recognition, synaptic differentiation and maturation of the synapse through processes of stabilization/destabilization. At the neuromuscular junction (NMJ), in some congenital myasthenic syndromes or autoimmune diseases, one of these steps is perturbed during development and leads to functional defects at the synaptic contact. These defects also appear in traumatic and frequently in postoperative peripheral nerve injuries. Regeneration of the nerve is slow and incomplete which underlines the necessity of finding treatments for this major pathology. To stimulate formation or regeneration of the synapse, one needs to understand the molecular and cellular bases for the establishment of such a specialized contact where the pre and post synaptic cells become precisely apposed and differentiate. Signals from the nerve and the muscle orchestrate the formation of the NMJ in a temporal sequence through a dynamic communication between the two cells. The identity of a number of these organizing signals is beginning to be revealed. Most of these signals are involved in synapse differentiation and maturation. However, the early step corresponding to target recognition is still “a black box”. We are investigating the signals that come from the muscle to instruct the growth cone of its final attachment site on the muscle. We focus on events that take place in the middle of the muscle where the nerve contacts the muscle. In this localization, a postsynaptic muscle specific tyrosine kinase called MuSK is expressed before innervation and is known to play a key role in the subsequent steps of synapse differentiation, maturation and maintenance. Our working hypothesis is that MuSK and a member of the Wnts, a family of axonal guidance molecules, play a major role in guiding growth cones to this muscle central zone. Elucidating the molecular mechanisms of synapse formation and maintenance will provide a basis for developing regenerative therapies for motoneuron and muscle damage.