A CRUCIAL ROLE FOR NEUROTROPHIN-3 IN OLIGODENDROCYTE DEVELOPMENT
A CRUCIAL ROLE FOR NEUROTROPHIN-3 IN OLIGODENDROCYTE DEVELOPMENT
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DOI：
10.1038/367371a0
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发表时间：
1994-01-27
期刊：
影响因子：
64.8
通讯作者：
BARDE, YA
中科院分区：
文献类型：
--
作者：
BARRES, BA;RAFF, MC;BARDE, YA
神经营养因子：神经生长因子、脑源性神经营养因子、神经营养因子-3和神经营养因子-4 /5可促进脊椎动物神经元亚群的体外存活，但迄今为止只有神经生长因子被证明对正常神经元发育至关重要1-4；以前没有神经营养因子被证明在正常的胶质细胞发育中起作用。我们最近发现，神经营养因子-3在体外促进纯少突胶质前体细胞的存活，虽然它本身只诱导一小部分细胞合成DNA，但与血小板衍生生长因子结合后，它诱导大多数细胞合成DNA 5。然而，这些因素都没有被证明有助于体内少突胶质前体细胞增殖或刺激这些细胞的纯群体体外增殖（与合成DNA相反）。本研究表明，神经营养因子-3和血小板衍生生长因子共同促进体外少突胶质前体细胞的克隆扩增，并驱动少突胶质细胞发育的内在时钟6。我们还表明，神经营养因子-3有助于刺激体内少突胶质前体细胞的增殖，因此是正常少突胶质细胞发育所必需的。
THE neurotrophins nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin4/5 promote the survival of subpopulations of vertebrate neurons in vitro, but so far only nerve growth factor has been demonstrated to be essential for normal neuronal development1-4; no neurotrophin has previously been shown to function in normal glial cell development. We found recently that neurotrophin-3 promotes the survival of pure oligodendrocyte precursor cells in vitro, and although by itself it induces only a small percentage of these cells to synthesize DNA, in combination with platelet-derived growth factor it induces the majority of them to do so5. Neither of these factors, however, has been shown to contribute to oligodendrocytes precursor cell proliferation in vivo or to stimulate pure populations of these cells to proliferate (as opposed to synthesize DNA) in vitro. Here we show that neurotrophin-3 and platelet-derived growth factor collaborate to promote clonal expansion of oligodendrocyte precursor cells in vitro and to drive the intrinsic clock that times oligodendrocyte development6. We also show that neurotrophin-3 helps stimulate the proliferation of oligodendrocyte precursor cells in vivo and is thus required for normal oligodendrocyte development.