β-catenin signaling promotes proliferation of progenitor cells in the adult mouse subventricular zone

Kazuhide Adachi, Zaman Mirzadeh, Masanori Sakaguchi, Toru Yamashita, Tania Nikolcheva, Yukiko Gotoh, Gary Peltz, Leyi Gong, Takeshi Kawase, Arturo Alvarez-Buylla, Hideyuki Okano, Kazunobu Sawamoto

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188 Citations (Scopus)

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/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.

Original languageEnglish
Pages (from-to)2827-2836
Number of pages10
JournalStem Cells
Volume25
Issue number11
DOIs
Publication statusPublished - 2007 Nov 1

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Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Adachi, K., Mirzadeh, Z., Sakaguchi, M., Yamashita, T., Nikolcheva, T., Gotoh, Y., Peltz, G., Gong, L., Kawase, T., Alvarez-Buylla, A., Okano, H., & Sawamoto, K. (2007). β-catenin signaling promotes proliferation of progenitor cells in the adult mouse subventricular zone. Stem Cells, 25(11), 2827-2836. https://doi.org/10.1634/stemcells.2007-0177