Martínez-Morales J R, Barbas J A, Martí E, Bovolenta P, Edgar D, Rodríguez-Tébar A
Instituto Cajal de Neurobiología, CSIC, Madrid, Spain.
Development. 1997 Dec;124(24):5139-47. doi: 10.1242/dev.124.24.5139.
The extracellular matrix protein vitronectin and its mRNA are present in the embryonic chick notochord, floor plate and in the ventral neural tube at the time position of motor neuron generation. When added to cultures of neural tube explants of developmental stage 9, vitronectin promotes the generation of motor neurons in the absence of either notochord or exogenously added Sonic hedgehog. Conversely, the neutralisation of endogenous vitronectin with antibodies inhibits over 90% motor neuron differentiation in co-cultured neural tube/notochord explants, neural tube explants cultured in the presence of Sonic hedgehog, and in committed (stage 13) neural tube explants. Furthermore, treatment of embryos with anti-vitronectin antibodies results in a substantial and specific reduction in the number of motor neurons generated in vivo. These results demonstrate that vitronectin stimulates the differentiation of motor neurons in vitro and in vivo. Since the treatment of stage 9 neural tube explants with Sonic hedgehog resulted in induction of vitronectin mRNA expression before the expression of floor plate markers, we conclude that vitronectin may act either as a downstream effector in the signalling cascade induced by Sonic hedgehog, or as a synergistic factor that increases Shh-induced motor neuron differentiation.
细胞外基质蛋白玻连蛋白及其mRNA在运动神经元产生时的胚胎鸡脊索、底板和腹侧神经管中存在。当添加到发育阶段9的神经管外植体培养物中时,玻连蛋白在既没有脊索也没有外源添加音猬因子的情况下促进运动神经元的产生。相反,用抗体中和内源性玻连蛋白会抑制共培养的神经管/脊索外植体、在音猬因子存在下培养的神经管外植体以及已分化(阶段13)的神经管外植体中超过90%的运动神经元分化。此外,用抗玻连蛋白抗体处理胚胎会导致体内产生的运动神经元数量大幅且特异性减少。这些结果表明玻连蛋白在体外和体内均刺激运动神经元的分化。由于用音猬因子处理阶段9的神经管外植体会在底板标志物表达之前诱导玻连蛋白mRNA表达,我们得出结论,玻连蛋白可能作为音猬因子诱导的信号级联反应中的下游效应物,或者作为增加音猬因子诱导的运动神经元分化的协同因子发挥作用。