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)
National Institute of Neurological Disorders and Stroke (NINDS)
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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Hollis 2nd, Edmund R; Ishiko, Nao; Yu, Ting et al. (2016) Ryk controls remapping of motor cortex during functional recovery after spinal cord injury. Nat Neurosci 19:697-705
Hollis 2nd, Edmund R; Ishiko, Nao; Tolentino, Kristine et al. (2015) A novel and robust conditioning lesion induced by ethidium bromide. Exp Neurol 265:30-9
Hollis 2nd, Edmund R; Ishiko, Nao; Pessian, Maysam et al. (2015) Remodelling of spared proprioceptive circuit involving a small number of neurons supports functional recovery. Nat Commun 6:6079
Onishi, Keisuke; Hollis, Edmund; Zou, Yimin (2014) Axon guidance and injury-lessons from Wnts and Wnt signaling. Curr Opin Neurobiol 27:232-40
Tury, Anna; Tolentino, Kristine; Zou, Yimin (2014) Altered expression of atypical PKC and Ryk in the spinal cord of a mouse model of amyotrophic lateral sclerosis. Dev Neurobiol 74:839-50
Onishi, Keisuke; Shafer, Beth; Lo, Charles et al. (2013) Antagonistic functions of Dishevelleds regulate Frizzled3 endocytosis via filopodia tips in Wnt-mediated growth cone guidance. J Neurosci 33:19071-85
Hollis 2nd, Edmund R; Zou, Yimin (2012) Reinduced Wnt signaling limits regenerative potential of sensory axons in the spinal cord following conditioning lesion. Proc Natl Acad Sci U S A 109:14663-8
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

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