i) Rho GTPase signalling and axon outgrowth

GTPases of the Rho family are molecular switches that are activated by guanine nucleotide exchange factors (GEF) and inactivated by GTPase-activating proteins (GAP). We and others have shown that the Rho GEF Trio is a major regulator of cell migration and axon outgrowth by controlling actin cytoskeleton remodelling through the activation of the Rho GTPase Rac1. We have recently uncovered an unexpected physical link between Trio and proteins involved in the control of microtubule (MT) dynamics, and we have demonstrated that Trio ability to bind to MTs is essential for its function in axon outgrowth. Our current work aims at deciphering the molecular mechanisms underlying the interplay between Trio, actin cytoskeleton remodelling, and MT dynamics during axon outgrowth.

ii) Rho GTPase signalling and synaptogenesis

In addition to axon outgrowth, Rho GTPases also participate in the morphogenesis of dendritic spines that form and establish synaptic contacts during brain development. We have recently identified new members of the Rho GTPase signalling cascade that contribute to the formation of dendritic spines, including the Rho GEF DOCK10. We are now studying the molecular mechanisms by which these proteins control this process. In addition, we are testing whether disruption of the function of these proteins contributes to the development of neuronal disorders.