The wiring of neuronal circuit relies on the accurate navigation of axons towards their targets. Aberrant connections during development can lead to major neurological disorders. The guidance signals that wire the brain are mostly known. However, how these cues are integrated and translated into microtubule/actin-based growth cone mechanical behaviors are largely unknown. Preliminary data suggest that Fidgetin-like 1, a microtubule-depolymerizing ATPase, acts as an integrator of repulsive cues that regulates both microtubule and actin dynamics to steer growing axons. (see Fassier C, et al. (2018) Motor axon navigation relies on Fidgetin-like 1-driven microtubule plus end dynamics. J Cell Biol 217(5):1719-1738). The project aims at exploring the role of Fidgetin-like 1 in cytoskeleton dynamics and decode how this ATPase coordinates microtubule/F-actin remodeling to control axon guidance and neuronal connectivity, in coordination with Dr. Coralie Fassier, Institut de la Vision, Paris, France. Using a set of cell-free assays combined with microscopy technics, the post-doctoral fellow will investigate how Fidgetin-like 1 control actin nucleation, dynamics and structural organization, and contribute to the crosstalk between actin and microtubule cytoskeletons.
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