Wnt-3a and Wnt-3 differently stimulate proliferation and neurogenesis of spinal neural precursors and promote neurite outgrowth by canonical signaling

David, Mónica Delia; Cantí Nicolás, Carles; Herreros Danés, Judit

doi:https://doi.org/10.1002/jnr.22464

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Issue date

2010

Author

David, Mónica Delia

Cantí Nicolás, Carles

Herreros Danés, Judit

Suggested citation

David, Mónica Delia; Cantí Nicolás, Carles; Herreros Danés, Judit; . (2010) . Wnt-3a and Wnt-3 differently stimulate proliferation and neurogenesis of spinal neural precursors and promote neurite outgrowth by canonical signaling. Journal of Neuroscience Research, 2010, vol. 88, núm. 14, p. 3011-3023. https://doi.org/10.1002/jnr.22464.

Abstract

Wnt factors regulate neural stem cell development and neuronal connectivity. Here we investigated whether Wnt-3a and Wnt-3, expressed in the developing spinal cord, regulate proliferation and the neuronal differentiation of spinal cord neural precursors (SCNP). Wnt-3a promoted a sustained increase of

SCNP proliferation, whereas Wnt-3 enhanced SCNP proliferation transiently and increased neurogenesis through β-catenin signaling. Consistent with this, Wnt-3a and Wnt-3 differently regulate the expression of Cyclin-dependent kinase inhibitors. Furthermore, Wnt-3a and Wnt-3 stimulated neurite outgrowth in SCNP-derived neurons through ß-catenin and TCF4-dependent transcription. GSK-3ß inhibitors mimicked Wnt signaling and promoted neurite outgrowth in established cultures. We conclude that Wnt-3a and Wnt-3 signal through the canonical Wnt/β-catenin pathway to regulate different aspects of SCNP development. These findings may be of therapeutic interest for the treatment of neurodegenerative diseases and nerve injury.

URI

http://hdl.handle.net/10459.1/47338

DOI

https://doi.org/10.1002/jnr.22464

Is part of

Journal of Neuroscience Research, 2010, vol. 88, núm. 14, p. 3011-3023