Frederick Terra J, Wood Teresa L
Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA 17033, USA.
Mol Cell Neurosci. 2004 Mar;25(3):480-92. doi: 10.1016/j.mcn.2003.11.015.
A critical question in developmental neurobiology is how stem and progenitor cells interpret multiple signals to decide whether to proliferate or exit the cell cycle. Insulin-like growth factor (IGF)-I and fibroblast growth factor (FGF)-2 have known functions individually in development of neural stem cells as well as more restricted neuronal and glial progenitor cells. The goal of this study was to elucidate how IGF-I and FGF-2 coordinately regulate the cell cycle machinery in primary oligodendrocyte progenitors (OPs). IGF-I/FGF-2 synergistically increased the numbers of OP cells recruited into S phase. IGF-I enhanced FGF-2 induction of cyclin D1, activation of G(1) cyclin-cyclin-dependent kinase (cdk) complexes, and hyperphosphorylation of retinoblastoma protein (pRb). Moreover, IGF-I was required for G(2)/M progression. In contrast, FGF-2 decreased levels of the cdk inhibitor p27(Kip1) associated with cyclin E-cdk2. These studies provide a mechanistic basis for coordinate regulation of cell cycle progression in progenitor cells by multiple growth factors.
发育神经生物学中的一个关键问题是，干细胞和祖细胞如何解读多种信号，以决定是进行增殖还是退出细胞周期。胰岛素样生长因子（IGF）-I和成纤维细胞生长因子（FGF）-2在神经干细胞以及更具特异性的神经元和神经胶质祖细胞的发育过程中各自具有已知的功能。本研究的目的是阐明IGF-I和FGF-2如何协同调节原代少突胶质细胞祖细胞（OPs）中的细胞周期机制。IGF-I/FGF-2协同增加了进入S期的OP细胞数量。IGF-I增强了FGF-2对细胞周期蛋白D1的诱导作用、G(1)期细胞周期蛋白-细胞周期蛋白依赖性激酶（cdk）复合物的激活以及视网膜母细胞瘤蛋白（pRb）的过度磷酸化。此外，G(2)/M期进程需要IGF-I。相反，FGF-2降低了与细胞周期蛋白E-cdk2相关的cdk抑制剂p27(Kip1)的水平。这些研究为多种生长因子对祖细胞中细胞周期进程的协同调节提供了机制基础。
