One of the most remarkable feats in early neural development occurs when each neuron sends out an axon tipped with a growth cone, which navigates through the embryonic terrain and interprets guidance cues to find and connect with its final target. Abnormalities in axon guidance are associated with a multitude of neurodevelopmental disorders, including autism and schizophrenia. Many decades of axon guidance research have defined key extracellular cues and signaling pathways for this process, yet we still do not understand how these cues translate into the coordinated cytoskeletal dynamics that drive the morphological responses (advance, retraction, and turning) of the growth cone.
A long-term goal of our lab is to understand how cytoskeletal coordination occurs in the embryonic growth cone. Specifically, we focus on the regulation of the plus-ends of microtubules (MTs), which play a key role in growth cone steering. An important feature of MT plus-ends is the presence of a conserved set of proteins called 'plus-end tracking proteins' (+TIPs) that localize to the plus-ends and regulate their behavior. Evidence suggests that +TIPs act in response to upstream guidance cues by coordinating the downstream MT response.
Our research utilizes high-resolution live imaging and computational analysis of cytoskeletal behavior in cultured Xenopus laevis embryonic neurons to answer the question of how +TIPs interact and function within the growth cone to drive directed cell motility.