期刊
CEREBRAL CORTEX
卷 22, 期 10, 页码 2415-2427出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhr320
关键词
beta-Catenin; Hipk1; Stem cells; SVZ; Wnt
资金
- BMW Italy group
- Italian Association for Multiple Sclerosis (Fism/Aism) [Stem cells 2008]
The canonical Wnt/Wingless pathway is implicated in regulating cell proliferation and cell differentiation of neural stem/progenitor cells. Depending on the context, beta-Catenin, a key mediator of the Wnt signaling pathway, may regulate either cell proliferation or differentiation. Here, we show that beta-Catenin signaling regulates the differentiation of neural stem/progenitor cells in the presence of the beta-Catenin interactor Homeodomain interacting protein kinase-1 gene (Hipk1). On one hand, Hipk1 is expressed at low levels during the entire embryonic forebrain development, allowing beta-Catenin to foster proliferation and to inhibit differentiation of neural stem/progenitor cells. On the other hand, Hipk1 expression dramatically increases in neural stem/progenitor cells, residing within the subventricular zone (SVZ), at the time when the canonical Wnt signaling induces cell differentiation. Analysis of mouse brains electroporated with Hipk1, and the active form of beta-Catenin reveals that coexpression of both genes induces proliferating neural stem/progenitor cells to escape the cell cycle. Moreover, in SVZ derive neurospheres cultures, the overexpression of both genes increases the expression of the cell-cycle inhibitor P16Ink4. Therefore, our data confirm that the beta-Catenin signaling plays a dual role in controlling cell proliferation/differentiation in the brain and indicate that Hipk1 is the crucial interactor able to revert the outcome of beta-Catenin signaling in neural stem/progenitor cells of adult germinal niches.
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