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TISSUE-SPECIFIC STEM CELLS

β-Catenin Signaling Promotes Proliferation of Progenitor Cells in the Adult Mouse Subventricular Zone

^aDepartment of Physiology,
^bBridgestone Laboratory of Developmental and Regenerative Neurobiology, and
^cDepartment of Neurosurgery, Keio University School of Medicine, Tokyo, Japan;
^dDepartment of Neurological Surgery and Program in Developmental and Stem Cell Biology, University of California San Francisco, San Francisco, California, USA;
^eDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan;
^fDepartments of Genetics and Genomics and
^gInstitute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan;
^hDepartment of Chemistry, Roche Palo Alto, Palo Alto, California, USA;
ⁱDepartment of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

Key Words. β-Catenin • Neurogenesis • Cell proliferation • Subventricular zone • Olfactory bulb • Mash1

Correspondence: Kazunobu Sawamoto, Ph.D., Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. Telephone: 81-52-853-8532; Fax: 81-52-851-1898; e-mail: sawamoto{at}med.nagoya-cu.ac.jp; Hideyuki Okano, M.D., Ph.D., Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Telephone: 81-3-5363-3747; Fax: 81-3-3357-5445; e-mail: hidokano{at}sc.itc.keio.ac.jp

Received on March 19, 2007; accepted for publication on July 23, 2007.

First published online in STEM CELLS EXPRESS  August 2, 2007.


The subventricular zone (SVZ) is the largest germinal zone in the mature rodent brain, and it continuously produces young neurons that migrate to the olfactory bulb. Neural stem cells in this region generate migratory neuroblasts via highly proliferative transit-amplifying cells. The Wnt/β-catenin signaling pathway partially regulates the proliferation and neuronal differentiation of neural progenitor cells in the embryonic brain. Here, we studied the role of β-catenin signaling in the adult mouse SVZ. β-Catenin-dependent expression of a destabilized form of green fluorescent protein was detected in progenitor cells in the adult SVZ of Axin2-d2EGFP reporter mice. Retrovirus-mediated expression of a stabilized β-catenin promoted the proliferation of Mash1+ cells and inhibited their differentiation into neuroblasts. Conversely, the expression of Dkk1, an inhibitor of Wnt signaling, reduced the proliferation of Mash1+ cells. In addition, an inhibitor of GSK3β promoted the proliferation of Mash1+ cells and increased the number of new neurons in the olfactory bulb 14 days later. These results suggest that β-catenin signaling plays a role in the proliferation of progenitor cells in the SVZ of the adult mouse brain.

Disclosure of potential conflicts of interest is found at the end of this article.

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