Downregulation of activating transcription factor 5 is required for differentiation of neural progenitor cells into astrocytes
Downregulation of activating transcription factor 5 is required for differentiation of neural progenitor cells into astrocytes
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DOI：
10.1523/jneurosci.3447-04.2005
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发表时间：
2005-04-13
影响因子：
5.3
通讯作者：
Greene, LA
中科院分区：
文献类型：
--
作者：
Angelastro, JM;Mason, JL;Greene, LA
调节神经祖细胞分化的机制主要是未知的。转录因子激活转录因子5（ATF5）在发育中的脑的神经祖细胞中表达，但在成熟的星形胶质细胞和神经元中不存在。在这里，我们证明了ATF5调节心室区（VZ）和室下区（SVZ）神经祖细胞转化为星形胶质细胞。组成型ATF5表达维持神经祖细胞增殖并阻断它们在体外和体内分化成星形胶质细胞。相反，ATF5功能的丧失促进细胞周期退出并允许体外和体内星形胶质细胞分化。CNTF是星形胶质细胞分化的启动子，下调内源性ATF5，而组成型表达的ATF5抑制CNTF促进的星形胶质细胞发生。出乎意料的是，在体外和体内新生SVZ细胞中的组成型ATF 5表达使它们获得VZ细胞的性质和解剖分布。这些发现确定了ATF5是星形胶质细胞形成的关键调节因子，并可能是VZ向SVZ转变的关键调节因子。
The mechanisms that regulate neural progenitor cell differentiation are primarily unknown. The transcription factor activating transcription factor 5 (ATF5) is expressed in neural progenitors of developing brain but is absent from mature astrocytes and neurons. Here, we demonstrate that ATF5 regulates the conversion of ventricular zone (VZ) and subventricular zone (SVZ) neural progenitors into astrocytes. Constitutive ATF5 expression maintains neural progenitor cell proliferation and blocks their in vitro and in vivo differentiation into astrocytes. Conversely, loss of ATF5 function promotes cell-cycle exit and allows astrocytic differentiation in vitro and in vivo. CNTF, a promoter of astrocytic differentiation, downregulates endogenous ATF5, whereas constitutively expressed ATF5 suppresses CNTF-promoted astrocyte genesis. Unexpectedly, constitutive ATF5 expression in neonatal SVZ cells both in vitro and in vivo causes them to acquire properties and anatomic distributions of VZ cells. These findings identify ATF5 as a key regulator of astrocyte formation and potentially of the VZ to SVZ transition.