CONICET | Buscador de Institutos y Recursos Humanos

Axonal pathﬁnding decisions rely on intercellular attractive and repulsive guidance cues which are read by guidance receptors present located in the navigating growth cones. Recently, the endocannabinoid (eCB) system has been identified as an important regulator of brain wiring during development with relevant roles in axonal outgrowth and pathfinding. eCBs mediate the motility and directional turning of a developing axons by activating CB1 cannabinoid receptors (CB1R) in its growth cone. Although cargo delivery are essential in developing neurons for molecule deliveripresentation ng molecules that are required for during elongation and guidance of the growing axonsal, the axonal transport system that mediate thise delivery of guidance receptors during the axon pathfinding remain mostly unknown. To test the hypothesis that CB1R function depends on kinesin-1 mediated anterograde delivery is required for the proper axonal guidance, we use mice lacking the kinesin light chain 1 (klc1) subunit of the anterograde motor kinesin-1. To test this hypothesis in vivo, we performed axon-tracing experiments with DiI in klc1-deficient mice and we found several axonal guidance defects in axonal tracts. Interestingly, Using live-cell imaging of CB1-GFP transfected neurons, we demonstrate revealed the dependency of at deletion of klc1 motor for normal CB1 receptor dynamics and positioning by live-cell imaging of CB1-GFP transfected neurons. klc1-/- showed motor protein results in a reduction of CB1R anterograde velocity and a decrease of anterograde and retrograde proportion of CB1R-GFP vesicles along axons. Finally, we demonstrated that Klc1 is required for the correct growth cone collapse and axonal outgrowth-induced by CB1R agonists. These Altogether, these results suggest that klc1 klc1-mediated transport of CB1R is required for a normal endocannabinoid signaling in the axonal pathfinding in of the developing brain