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.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
2R01NS047484-11A1
Application #
8750209
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Riddle, Robert D
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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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
Zou, Yimin (2011) When it is hard to get to with genetics--planar cell polarity under a chemical scalpel. Chem Biol 18:1350-1
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
Liu, Yaobo; Wang, Xiaofei; Lu, Chin-Chun et al. (2008) Repulsive Wnt signaling inhibits axon regeneration after CNS injury. J Neurosci 28:8376-82