Novitch Bennett G, Wichterle Hynek, Jessell Thomas M, Sockanathan Shanthini
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Center for Neurobiology and Behavior, Columbia University, 701 West 168th Street, New York, NY 10032, USA.
Neuron. 2003 Sep 25;40(1):81-95. doi: 10.1016/j.neuron.2003.08.006.
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 HD 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.
脊髓腹侧神经元命运的特化取决于音猬因子（Shh）对同源结构域（HD）蛋白和碱性螺旋-环-螺旋（bHLH）蛋白的调控。这些转录因子大多发挥阻遏作用，因此，诱导信号通路与参与腹侧神经元特化的转录激活因子之间的联系仍不清楚。我们在此表明，视黄酸信号及视黄酸受体的激活功能对于HD和bHLH蛋白的表达模式形成以及运动神经元特性的特化是必需的。我们还表明，成纤维细胞生长因子（FGFs）可抑制祖细胞HD蛋白的表达，这意味着逃避FGF信号并暴露于视黄酸和Shh信号是腹侧神经模式形成过程中的必要步骤。此外，神经祖细胞同时暴露于视黄酸和FGFs足以以不依赖Shh的方式诱导运动神经元分化。
