A requirement for retinoic acid-mediated transcriptional activation in ventral neural patterning and motor neuron specification
A requirement for retinoic acid-mediated transcriptional activation in ventral neural patterning and motor neuron specification
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DOI：
10.1016/j.neuron.2003.08.006
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发表时间：
2003-09-25
期刊：
影响因子：
16.2
通讯作者：
Sockanathan, S
中科院分区：
文献类型：
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作者：
Novitch, BG;Wichterle, H;Sockanathan, S
腹侧脊髓神经元命运的规范取决于音刺猬 (Shh) 对同源域 (HD) 和碱性螺旋环螺旋 (bHLH) 蛋白的调节。这些转录因子中的大多数都起到抑制因子的作用，导致诱导信号通路和参与腹侧神经元规范的转录激活因子之间的联系尚未解决。我们在此表明，类视黄醇信号传导和类视黄醇受体的激活剂功能对于 HD 和 bHLH 蛋白的表达模式以及指定运动神经元身份是必需的。我们还表明，成纤维细胞生长因子（FGF）抑制祖细胞 HID 蛋白的表达，这意味着逃避 FGF 信号以及暴露于类维生素A和Shh信号是腹侧神经模式出现的必然步骤。此外，神经祖细胞联合暴露于类维生素A和FGF足以以不依赖于Shh的方式诱导运动神经元分化。
The specification of neuronal fates in the ventral spinal cord depends on the regulation of homeodomain (HD) and basic-helix-loop-helix (bHLH) proteins by Sonic hedgehog (Shh). Most of these transcription factors function as repressors, leaving unresolved the link between inductive signaling pathways and transcriptional activators involved in ventral neuronal specification. We show here that retinoid signaling and the activator functions of retinoid receptors are required to pattern the expression of HD and bHLH proteins and to specify motor neuron identity. We also show that fibroblast growth factors (FGFs) repress progenitor HID protein expression, implying that evasion of FGF signaling and exposure to retinoid and Shh signals are obligate steps in the emergence of ventral neural pattern. Moreover, joint exposure of neural progenitors to retinoids and FGFs suffices to induce motor neuron differentiation in a Shh-independent manner.