Regulation of neurogenesis by Fgf8a requires Cdc42 signaling and a novel Cdc42 effector protein.
Regulation of neurogenesis by Fgf8a requires Cdc42 signaling and a novel Cdc42 effector protein.
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FGF8A对神经发生的调节需要CDC42信号传导和新型的CDC42效应蛋白。
DOI：
10.1016/j.ydbio.2013.08.020
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发表时间：
2013-10-15
影响因子：
2.7
通讯作者：
Houston, Douglas W.
中科院分区：
文献类型：
--
作者：
Hulstrand, Alissa M.;Houston, Douglas W.
成纤维细胞生长因子（FGF）信号传导是神经发育的许多方面所需的，包括神经诱导、CNS模式化和神经发生。FGF激活Ras/MAPK信号传导的能力被认为对这些功能至关重要。然而，MAPK信号传导不太可能完全解释FGF反应的多样性。我们的特点是Cdc 42依赖的信号通路下游的FGF 8a剪接异构体。我们发现，Cdc 42效应4样蛋白（Cdc 42 ep 4-l或Cep 4l）在非洲爪蟾胚胎中具有强大的神经元诱导活性。此外，我们发现，Cep 41和Cdc 42本身是必要的和足够的感觉神经发生在体内。此外，这两种蛋白质都参与Fgf 8a诱导的神经元诱导，并且Cdc 42/Cep 41缔合由Fgf 8的Fgf 8a同种型特异性促进，但不受缺乏神经元诱导活性的Fgf 8b促进。总体而言，这些数据表明Cdc 42在脊椎动物神经元发育所必需的Fgf 8a特异性信号通路中的新作用。
Fibroblast Growth Factor (FGF) signaling is required for numerous aspects of neural development, including neural induction, CNS patterning and neurogenesis. The ability of FGFs to activate Ras/MAPK signaling is thought to be critical for these functions. However, it is unlikely that MAPK signaling can fully explain the diversity of responses to FGFs. We have characterized a Cdc42-dependent signaling pathway operating downstream of the Fgf8a splice isoform. We show that a Cdc42 effector 4-like protein (Cdc42ep4-l or Cep4l) has robust neuronal-inducing activity in Xenopus embryos. Furthermore, we find that Cep4l and Cdc42 itself are necessary and sufficient for sensory neurogenesis in vivo. Furthermore, both proteins are involved in Fgf8a-induced neuronal induction, and Cdc42/Cep4l association is promoted specifically by the Fgf8a isoform of Fgf8, but not by Fgf8b, which lacks neuronal inducing activity. Overall, these data suggest a novel role for Cdc42 in an Fgf8a-specific signaling pathway essential for vertebrate neuronal development.
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影响因子：
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