A second major goal of the lab is to understand how axons navigate to their targets to form the circuitry of the nervous system. During development, extracellular guidance cues are received and integrated by axonal growth cones which, in turn, coordinate the cytoskeletal remodeling required for migration to their targets. Growth cone filopodia, comprised of F-actin bundles, extend and sample the environment. The Ena/VASP protein family, comprised of Mena, VASP and EVL, is required for axon guidance and, in turn, regulates the assembly of F-actin networks to favor filopodia formation and elongation. Ena/VASP are targets of several signaling pathways involved in neuronal migration and axon guidance, yet it is still unclear how Ena/VASP function is linked to guidance receptors. Furthermore, Ena/VASP function is implicated in both attraction and repulsion, raising the interesting question of how molecules that promote actin polymerization and filopodia formation function during growth cone repulsion. Our global hypothesis is that Ena/VASP acts as a convergence point downstream of multiple guidance cues that regulates cytoskeletal responses.
Mena (green) and actin (red) in a stage 1 cortical neuron.
Mena (green) and actin (red) in a growth cone.