期刊
DEVELOPMENTAL NEUROBIOLOGY
卷 67, 期 10, 页码 1348-1361出版社
JOHN WILEY & SONS INC
DOI: 10.1002/dneu.20506
关键词
adult neural hippocampal progenitor; proliferation; differentiation; PI3K/Akt; CREB
资金
- NINDS NIH HHS [NS058248] Funding Source: Medline
The phosphoinositide 3-OH kinase (PI3K)/Akt pathway has been implicated in regulating several important cellular processes, including apoptosis, survival, proliferation, and metabolism. Using both pharmacological and genetic means, we demonstrate here that PI3K/Akt plays a crucial role in the proliferation of adult hippocampal neural progenitor cells. PI3K/ Akt transduces intracellular signals from multiple mitogens, including basic fibroblast growth factor (FGF-2), Sonic hedgehog (Shh), and insulin-like growth factor I (IGF-1). In addition, retroviral vector-mediated overexpression of wild type Akt increased cell proliferation, while a dominant negative Akt inhibited proliferation. Furthermore, wild type Akt over-expression reduced glial (GFAP) and neuronal (beta-tubulin III) marker expression during differentiation, indicating that it inhibits cell differentiation. We also show that activation of the cAMP response element binding protein (CREB), which occurs in cells stimulated by FGF-2, is limited when Akt signaling is inhibited, demonstrating a link between Akt and CREB. Over-expression of wild type CREB increases progenitor proliferation, whereas dominant negative CREB only slightly decreases proliferation. These results indicate that PI3K/Akt signaling integrates extracellular signaling information to promote cellular proliferation and inhibit differentiation in adult neural progenitors. (C) 2007 Wiley Periodicals, Inc.
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