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

¹ Department of Physiology, Bridgestone Laboratory of Developmental and Regenerative Neurobiology, and Department of Neurosurgery, Keio University School of Medicine, Tokyo 160-8582, Japan
² Department of Neurological Surgery and Program in Developmental and Stem Cell Biology, University of California San Francisco, San Francisco, CA 94143, USA
³ Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan
⁴ Department of Physiology, Bridgestone Laboratory of Developmental and Regenerative Neurobiology, Keio University School of Medicine, Tokyo 160-8582, Japan, Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
⁵ Department of Genetics and Genomics, Roche Palo Alto, Palo Alto CA 94304, USA
⁶ Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan
⁷ Chemistry, Roche Palo Alto, Palo Alto CA 94304, USA
⁸ Department of Neurosurgery, Keio University School of Medicine, Tokyo 160-8582, Japan
⁹ Department of Physiology, Bridgestone Laboratory of Developmental and Regenerative Neurobiology, Keio University School of Medicine, Tokyo 160-8582, Japan, Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

^* To whom correspondence should be addressed. E-mail: sawamoto{at}med.nagoya-cu.ac.jp.

	Abstract

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/-catenin signaling pathway partially regulates the proliferation and neuronal differentiation of neural progenitor cells in the embryonic brain. Here, we studied the role of -catenin signaling in the adult mouse SVZ. -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 -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 GSK3 promoted the proliferation of Mash1+ cells, and increased the number of new neurons in the olfactory bulb 14 days later. These results suggest that -catenin signaling plays a role in the proliferation of progenitor cells in the SVZ of the adult mouse brain.

Key Words. -catenin, neurogenesis, cell proliferation, subventricular zone, olfactory bulb, Mash1

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