FGF-receptor signalling controls neural cell diversity in the zebrafish hindbrain by regulating olig2 and sox9
FGF-receptor signalling controls neural cell diversity in the zebrafish hindbrain by regulating olig2 and sox9
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DOI：
10.1242/dev.038026
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发表时间：
2010-01-01
期刊：
影响因子：
4.6
通讯作者：
Ghislain, Julien
中科院分区：
文献类型：
--
作者：
Esain, Virginie;Postlethwait, John H.;Ghislain, Julien
神经细胞多样性产生的机制是深入研究的主题，其中强调了包括Shh、BMP和Wnt在内的不同信号分子的参与。相比之下，人们对 FGF 在此过程中的了解相对较少。在本报告中，我们确定了斑马鱼后脑神经祖细胞中的 FGF 受体依赖性途径，该途径产生体细胞运动神经元、少突胶质细胞祖细胞和分化星形胶质细胞。我们结合化学和遗传方法来有条件地灭活 FGF 受体信号传导，研究了该途径的作用。我们表明，FGF 受体信号传导对于后脑神经祖细胞的生存或维持并不是必需的，而是通过协调调节关键转录因子来控制其命运。首先，通过与Shh合作，FGF受体信号传导控制olig2的表达，olig2是体细胞运动神经元和少突胶质细胞规范所必需的模式基因。其次，FGF 受体信号传导通过调节 sox9 来控制少突胶质细胞祖细胞和星形胶质细胞的发育，sox9 是一种胶质生成转录因子，我们证明其功能在斑马鱼后脑中是保守的。总的来说，我们的结果首次在体内揭示了 FGF 控制神经细胞多样性的机制。
The mechanisms underlying the generation of neural cell diversity are the subject of intense investigation, which has highlighted the involvement of different signalling molecules including Shh, BMP and Wnt. By contrast, relatively little is known about FGF in this process. In this report we identify an FGF-receptor-dependent pathway in zebrafish hindbrain neural progenitors that give rise to somatic motoneurons, oligodendrocyte progenitors and differentiating astroglia. Using a combination of chemical and genetic approaches to conditionally inactivate FGF-receptor signalling, we investigate the role of this pathway. We show that FGF-receptor signalling is not essential for the survival or maintenance of hindbrain neural progenitors but controls their fate by coordinately regulating key transcription factors. First, by cooperating with Shh, FGF-receptor signalling controls the expression of olig2, a patterning gene essential for the specification of somatic motoneurons and oligodendrocytes. Second, FGF-receptor signalling controls the development of both oligodendrocyte progenitors and astroglia through the regulation of sox9, a gliogenic transcription factor the function of which we show to be conserved in the zebrafish hindbrain. Overall, for the first time in vivo, our results reveal a mechanism of FGF in the control of neural cell diversity.