Specification of astrocytes by bHLH protein SCL in a restricted region of the neural tube
Specification of astrocytes by bHLH protein SCL in a restricted region of the neural tube
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DOI：
10.1038/nature04139
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发表时间：
2005-11-17
期刊：
影响因子：
64.8
通讯作者：
Rowitch, DH
中科院分区：
文献类型：
--
作者：
Muroyama, Y;Fujiwara, Y;Rowitch, DH
星形胶质细胞是脊椎动物中枢神经系统（CNS）中最丰富和功能多样的胶质细胞群（1）。然而，星形胶质细胞特化的潜在机制知之甚少。已经确定，胚胎中神经元的细胞多样化是由位置依赖性外在信号和转录因子的组合相互作用产生的，这些转录因子通过抑制替代命运来指导特定的细胞命运（2）。目前还不清楚是否有类似的过程决定胚胎星形胶质细胞的身份。事实上，星形胶质细胞的发育通常被认为是以位置独立的方式发生的（3，4）。在这里，我们显示了多种功能的干细胞白血病（Scl，也被称为Tal 1），它编码一个基本的螺旋-环-螺旋（bHLH）转录因子，在调节星形胶质细胞与少突胶质细胞的细胞命运收购和V2 b与V2 a中间神经元细胞的命运收购在p2结构域的脊椎动物脊髓的发展。我们的研究结果表明，星形胶质细胞和V2 b中间神经元发育所必需的区域限制性转录程序，与SCL参与造血有惊人的相似之处。他们进一步表明，胚胎胶质细胞亚型身份的获得可能受到SCL和腹侧神经管中转录因子Olig 2之间的遗传相互作用的调节。
Astrocytes are the most abundant and functionally diverse glial population in the vertebrate central nervous system (CNS)(1). However, the mechanisms underlying astrocyte specification are poorly understood. It is well established that cellular diversification of neurons in the embryo is generated by position-dependent extrinsic signals and combinatorial interactions of transcription factors that direct specific cell fates by suppressing alternative fates(2). It is unknown whether a comparable process determines embryonic astrocyte identity. Indeed, astrocyte development is generally thought to take place in a position-independent manner(3,4). Here we show multiple functions of Stem cell leukaemia (Scl, also known as Tal1), which encodes a basic helix-loop-helix (bHLH) transcription factor, in the regulation of both astrocyte versus oligodendrocyte cell fate acquisition and V2b versus V2a interneuron cell fate acquisition in the p2 domain of the developing vertebrate spinal cord. Our findings demonstrate a regionally restricted transcriptional programme necessary for astrocyte and V2b interneuron development, with striking parallels to the involvement of SCL in haematopoiesis. They further indicate that acquisition of embryonic glial subtype identity might be regulated by genetic interactions between SCL and the transcription factor Olig2 in the ventral neural tube.