Premium
Wnt‐3a and Wnt‐3 differently stimulate proliferation and neurogenesis of spinal neural precursors and promote neurite outgrowth by canonical signaling
Author(s) -
David Monica D.,
Cantí Carles,
Herreros Judit
Publication year - 2010
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22464
Subject(s) - wnt signaling pathway , neurogenesis , neurite , neural stem cell , microbiology and biotechnology , lrp6 , gsk 3 , dkk1 , biology , neural development , beta catenin , catenin , stem cell , lrp5 , neuroscience , signal transduction , biochemistry , gene , in vitro
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 and decreased the expression of cyclin‐dependent kinase inhibitors. In contrast, Wnt‐3 transiently enhanced SCNP proliferation and increased neurogenesis through β‐catenin signaling. Furthermore, both Wnt‐3a and Wnt‐3 stimulated neurite outgrowth in SCNP‐derived neurons through β‐catenin‐ and TCF4‐dependent transcription. Glycogen synthase kinase‐3β inhibitors mimicked Wnt signaling and promoted neurite outgrowth in established cultures. We conclude that Wnt‐3a and Wnt‐3 factors 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. © 2010 Wiley‐Liss, Inc.