Developmental Neurobiology, Medical Research Council-National Institute for Medical Research, London NW71AA, United Kingdom.
Genes Dev. 2010 Jun 1;24(11):1186-200. doi: 10.1101/gad.559910.
The secreted ligand Sonic Hedgehog (Shh) organizes the pattern of cellular differentiation in the ventral neural tube. For the five neuronal subtypes, increasing levels and durations of Shh signaling direct progenitors to progressively more ventral identities. Here we demonstrate that this mode of action is not applicable to the generation of the most ventral cell type, the nonneuronal floor plate (FP). In chick and mouse embryos, FP specification involves a biphasic response to Shh signaling that controls the dynamic expression of key transcription factors. During gastrulation and early somitogenesis, FP induction depends on high levels of Shh signaling. Subsequently, however, prospective FP cells become refractory to Shh signaling, and this is a prerequisite for the elaboration of their identity. This prompts a revision to the model of graded Shh signaling in the neural tube, and provides insight into how the dynamics of morphogen signaling are deployed to extend the patterning capacity of a single ligand. In addition, we provide evidence supporting a common scheme for FP specification by Shh signaling that reconciles mechanisms of FP development in teleosts and amniotes.
分泌的配体 Sonic Hedgehog(Shh)在腹侧神经管中组织细胞分化的模式。对于五种神经元亚型,Shh 信号的增加水平和持续时间指导祖细胞逐渐向更腹侧的身份发展。在这里,我们证明这种作用模式不适用于产生最腹侧的细胞类型,即非神经元基板(Floor Plate,FP)。在鸡和鼠胚胎中,FP 的特化涉及 Shh 信号的双相反应,控制关键转录因子的动态表达。在原肠胚形成和早期体节形成期间,FP 的诱导取决于高水平的 Shh 信号。然而,随后,潜在的 FP 细胞对 Shh 信号产生抗性,这是它们身份特化的前提条件。这促使我们对神经管中分级 Shh 信号模型进行了修订,并深入了解了形态发生素信号的动态如何被用来扩展单个配体的模式形成能力。此外,我们提供了支持 Shh 信号通过共同方案来指定 FP 的证据,这使得我们能够协调硬骨鱼类和羊膜动物中 FP 发育的机制。