Although many axon guidance molecules have been identified, the signaling and cell biological mechanisms leading to directed axon growth are still poorly understood. Building on our progress, we will ask in-depth questions about novel signaling and cell biological mechanisms of axon guidance. Specifically, we will use Frizzled3 phosphorylation and trafficking as a tool to solve how signaling asymmetry is generated in the growth cone and the cell biological mechanisms involved in turning. We will also use genetic mosaic approaches to study axon-axon interactions to address the unanswered question of how a group of axons pathfind together.

Public Health Relevance

This study proposes to discover novel signaling and cell biological mechanisms of axon guidance in development of functional circuits. These studies will provide basic scientific basis for therapeutic designs for neural circuit repair.

National Institute of Health (NIH)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Riddle, Robert D
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University of California San Diego
Schools of Arts and Sciences
La Jolla
United States
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Onishi, Keisuke; Hollis, Edmund; Zou, Yimin (2014) Axon guidance and injury-lessons from Wnts and Wnt signaling. Curr Opin Neurobiol 27:232-40
Shafer, Beth; Onishi, Keisuke; Lo, Charles et al. (2011) Vangl2 promotes Wnt/planar cell polarity-like signaling by antagonizing Dvl1-mediated feedback inhibition in growth cone guidance. Dev Cell 20:177-91
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Fenstermaker, Ali G; Prasad, Asheeta A; Bechara, Ahmad et al. (2010) Wnt/planar cell polarity signaling controls the anterior-posterior organization of monoaminergic axons in the brainstem. J Neurosci 30:16053-64
Wolf, Alex M; Lyuksyutova, Anna I; Fenstermaker, Ali G et al. (2008) Phosphatidylinositol-3-kinase-atypical protein kinase C signaling is required for Wnt attraction and anterior-posterior axon guidance. J Neurosci 28:3456-67
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