Developmental Neurobiology, MRC-National Institute for Medical Research, London, United Kingdom.
PLoS Biol. 2010 Jun 1;8(6):e1000382. doi: 10.1371/journal.pbio.1000382.
Morphogens are secreted signalling molecules that act in a graded manner to control the pattern of cellular differentiation in developing tissues. An example is Sonic hedgehog (Shh), which acts in several developing vertebrate tissues, including the central nervous system, to provide positional information during embryonic patterning. Here we address how Shh signalling assigns the positional identities of distinct neuronal subtype progenitors throughout the ventral neural tube. Assays of intracellular signal transduction and gene expression indicate that the duration as well as level of signalling is critical for morphogen interpretation. Progenitors of the ventral neuronal subtypes are established sequentially, with progressively more ventral identities requiring correspondingly higher levels and longer periods of Shh signalling. Moreover, cells remain sensitive to changes in Shh signalling for an extended time, reverting to antecedent identities if signalling levels fall below a threshold. Thus, the duration of signalling is important not only for the assignment but also for the refinement and maintenance of positional identity. Together the data suggest a dynamic model for ventral neural tube patterning in which positional information corresponds to the time integral of Shh signalling. This suggests an alternative to conventional models of morphogen action that rely solely on the level of signalling.
形态发生素是分泌的信号分子，以分级的方式作用，控制发育组织中细胞分化的模式。一个例子是 Sonic hedgehog（Shh），它在包括中枢神经系统在内的几个发育中的脊椎动物组织中起作用，为胚胎模式形成过程中提供位置信息。在这里，我们研究了 Shh 信号如何在整个腹侧神经管中分配不同神经元亚型祖细胞的位置身份。细胞内信号转导和基因表达的测定表明，信号的持续时间和水平对于形态发生素的解释至关重要。腹侧神经元亚型的祖细胞是依次建立的，腹侧身份越靠前，需要相应更高的水平和更长的 Shh 信号持续时间。此外，细胞对 Shh 信号变化的敏感性持续时间很长，如果信号水平低于阈值，细胞会恢复到先前的身份。因此，信号的持续时间不仅对于分配很重要，而且对于位置身份的细化和维持也很重要。这些数据共同表明了一种用于腹侧神经管模式形成的动态模型，其中位置信息对应于 Shh 信号的时间积分。这为仅依赖于信号水平的形态发生素作用的传统模型提供了一种替代方案。
