WNT Signaling in Central Nervous System Regeneration
Yimin Zou, Ph.D., UCSD
Associate Professor, Division of Biological Sciences, Section of Neurobiology
Edmund Hollis II, Ph.D.,
Zou Lab post-doctoral fellow

Injuries in the mature nervous system often result in permanent functional deficits. Very little is known about the mechanisms underlying the lack of plasticity and therefore it is hard to intervene effectively to improve quality of life for patients. We found that the Wnt family proteins and their receptors, Ryk and Frizzleds, are reinduced after spinal cord injury caused by hemisection and may regulate the regeneration of the corticospinal tract axons. Blocking Wnt-Ryk interaction prevented corticospinal tract axon retraction from the lesion site and promoted sprouting of collateral branches at and beyond the lesion site. The Wnt family proteins are important axon guidance molecules, which play pivotal roles in axonal path finding and axon target selection during development. Wnts are secreted glycoproteins and bind to transmembrane receptors, such as Frizzled, Ryk and Ror2. Preliminary results in the lab showed that upon sciatic nerve crush of adult rats, several genes encoding components of the Wnt signaling pathway, Wnts, Ryk and Frizzleds, are quickly induced in the dorsal root ganglion cell bodies and the axonal fibers in the dorsal roots. We also found that the adult dorsal root ganglion neurons from conditioning lesioned
animals respond to Wnt4, which induces neurite outgrowth, while uninjured control adult DRG neurons do not. Therefore, Wnt signaling may be a major mediator of the well-documented conditioning lesion response. We propose to study the role of Wnt signaling in the adult sensory axon response to injury and regeneration. This study will provide therapeutic tools for promoting axon regeneration in the spinal cord.

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