Combinatorial Gli Gene Function in Floor Plate and Neuronal Inductions by Sonic Hedgehog
Combinatorial Gli Gene Function in Floor Plate and Neuronal Inductions by Sonic Hedgehog
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作者：
A. R. I. Altaba
在发育中的脊椎动物神经系统中，尚不知道祖细胞如何解释诱导信号提供的位置信息，也不知道不同神经细胞群分化的区域如何定义。Gli蛋白可能参与这些过程。在青蛙的神经板，我们以前已经表明，锌指转录因子Gli 1在中线细胞中表达，并介导的Shh诱导底板分化的影响。相反，Gli 2和Gli 3在除中线外的整个神经板中表达。在这里，它表明，Gli 3和Shh相互抑制，而Gli 2，像Gli 1一样，是Shh信号的目标。然而，只有Gli 1可以诱导地板细胞的分化。此外，在共注射试验中，Gli 2和Gli 3抑制Gli 1对底板细胞的异位诱导，并抑制内源性底板分化。因此，底板结构域的定义似乎是由Gli 2和Gli 3对Gli 1功能的拮抗活性定义的。由于Gli 1和Gli 2都是由Shh诱导的，这些结果建立了一个由Shh触发的调节反馈回路，将底板细胞限制在中线。我们以前也表明，Gli基因诱导神经元分化，在这里，它表明，有特异性的神经元类型的Gli蛋白诱导。只有Gli 1诱导Nkx2.1/TTF-1（+）腹侧前脑神经元。此外，Gli 2和Gli 3抑制它们的分化。相反，脊髓运动神经元的分化可以由两个腹侧表达的Gli基因Gli 1和Gli 2诱导，表明Gli 2直接介导Shh对运动神经元的诱导。此外，Gli 3通过Gli 2抑制运动神经元分化。因此，组合Gli功能可以图案化神经管，整合位置信息和细胞类型分化。
Within the developing vertebrate nervous system, it is not known how progenitor cells interpret the positional information provided by inducing signals or how the domains in which distinct groups of neural cells differentiate are defined. Gli proteins may be involved in these processes. In the frog neural plate, we have previously shown that the zinc finger transcription factor Gli1 is expressed in midline cells and mediates the effects of Shh inducing floor plate differentiation. In contrast, Gli2 and Gli3 are expressed throughout the neural plate except for the midline. Here, it is shown that Gli3 and Shh repress each other whereas Gli2, like Gli1, is a target of Shh signaling. However, only Gli1 can induce the differentiation of floor plate cells. In addition, Gli2 and Gli3 repress the ectopic induction of floor plate cells by Gli1 in co-injection assays and inhibit endogenous floor plate differentiation. The definition of the floor plate domain, therefore, appears to be defined by the antagonizing activities of Gli2 and Gli3 on Gli1 function. Because both Gli1 and Gli2 are induced by Shh, these results establish a regulatory feedback loop triggered by Shh that restricts floor plate cells to the midline. We have also previously shown that the Gli genes induce neuronal differentiation and here it is shown that there is specificity to the types of neurons the Gli proteins induce. Only Gli1 induces Nkx2.1/TTF-1(+) ventral forebrain neurons. Moreover, Gli2 and Gli3 inhibit their differentiation. In contrast, the differentiation of spinal motor neurons can be induced by the two ventrally expressed Gli genes, Gli1 and Gli2, suggesting that Gli2 directly mediates induction of motor neurons by Shh. In addition, Gli3 inhibits motor neuron differentiation by Gli2. Thus, combinatorial Gli function may pattern the neural tube, integrating positional information and cell type differentiation.