Ebf gene function is required for coupling neuronal differentiation and cell cycle exit
Ebf gene function is required for coupling neuronal differentiation and cell cycle exit
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DOI：
10.1242/dev.00840
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发表时间：
2003-12-01
期刊：
影响因子：
4.6
通讯作者：
Charnay, P
中科院分区：
文献类型：
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作者：
Garcia-Dominguez, M;Poquet, C;Charnay, P
Ebf/Olf1家族的螺旋-环-螺旋转录因子先前被认为参与非洲爪蟾和小鼠中枢神经系统神经发生的控制，但其确切作用仍不清楚。我们对雏鸡中的两个家庭成员进行了表征，并通过功能获得和丧失实验进行了功能分析。这项研究揭示了 Ebf 基因在高等脊椎动物脊髓和后脑区域的几个特定作用，并使其能够沿着神经发生级联精确定位。在神经发生过程中，细胞周期退出似乎与迁移到地幔层和神经元分化紧密相关。我们发现拮抗 Ebf 基因活性可以解偶联这些过程。 Ebf 基因功能对于神经上皮祖细胞中启动神经元分化和向套层迁移是必需的，但对于细胞周期退出来说不是必需的。因此，Ebf 基因似乎是神经元分化和迁移的主控制器，将它们与细胞周期退出和神经发生的早期步骤耦合起来。原神经基因和 Ebf 基因之间的相互激活表明，除了参与分化之外，Ebf 基因还可能参与稳定状态。最后，功能获得数据提出了这样一种可能性：除了这些一般作用之外，Ebf 基因可能还参与中枢神经系统特定区域的神经元亚型规范。
Helix-loop-helix transcription factors of the Ebf/Olf1 family have previously been implicated in the control of neurogenesis in the central nervous system in both Xenopus laevis and the mouse, but their precise roles have remained unclear. We have characterised two family members in the chick, and have performed a functional analysis by gain- and loss-of-function experiments. This study revealed several specific roles for Ebf genes in the spinal cord and hindbrain regions of higher vertebrates, and enabled their precise positioning along the neurogenic cascade.During neurogenesis, cell cycle exit appears to be tightly coupled to migration to the mantle layer and to neuronal differentiation. We show that antagonizing Ebf gene activity allows the uncoupling of these processes. Ebf gene function is necessary to initiate neuronal differentiation and migration toward the mantle layer in neuroepithelial progenitors, but it is not required for cell cycle exit. Ebf genes therefore appear to be master controllers of neuronal differentiation and migration, coupling them to cell cycle exit and earlier steps of neurogenesis.Mutual activation between proneural and Ebf genes suggests that besides their involvement in the engagement of differentiation, Ebf genes may also participate in the stabilisation of the committed state. Finally, gain-of-function data raise the possibility that, in addition to these general roles, Ebf genes may be involved in neuronal subtype specification in particular regions of the CNS.