Control of cell pattern in the neural tube by the zinc finger transcription factor and oncogene Gli-1
Control of cell pattern in the neural tube by the zinc finger transcription factor and oncogene Gli-1
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DOI：
10.1016/s0896-6273(00)80344-x
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发表时间：
1997-07-01
期刊：
影响因子：
16.2
通讯作者：
Rosenthal, A
中科院分区：
文献类型：
--
作者：
Hynes, M;Stone, DM;Rosenthal, A
Sonic hedgehog（Shh）是由底板和脊索分泌的一种假定的形态发生素，其指定脊椎动物神经系统腹侧方面的多种细胞类型的命运。由于在果蝇中的行动Hh已被证明是由Cubitus interruptus（Ci），锌指转录因子转导，我们研究了这种蛋白质的脊椎动物同源物是否可以介导的脊椎动物神经系统中的Shh的功能。在这里，我们表明，表达的GLI-1，三个脊椎动物同源词，可以诱导Shh在神经管。此外，Gli-1在转基因小鼠的背侧中脑和后脑中的异位表达模拟了异位表达的Shh-N的作用，导致腹侧神经管标记物如Ptc、HNF-3 β和Shh的激活;导致背侧标记物如Pax-3和AL-1的抑制;以及导致多巴胺能和多巴胺能神经元的异位背侧簇的形成。这些研究结果表明，GLI-1可以再现神经系统发育中Shh的细胞模式化作用，并为它是脊椎动物Shh信号的介导者的假设提供支持。
Sonic hedgehog (Shh) is a putative morphogen secreted by the floor plate and notochord, which specifies the fate of multiple cell types in the ventral aspect of the vertebrate nervous system. Since in Drosophila the actions of Hh have been shown to be transduced by Cubitus interruptus (Ci), a zinc finger transcription factor, we examined whether a vertebrate homolog of this protein can mediate the functions of Shh in the vertebrate nervous system. Here, we demonstrate that expression of Gli-1, one of three vertebrate homologs of Ci, can be induced by Shh in the neural tube. Further, ectopic expression of Gli-1 in the dorsal midbrain and hindbrain of transgenic mice mimics the effects of ectopically expressed Shh-N, leading to the activation of ventral neural tube markers such as Ptc, HNF-3 beta, and Shh; to the suppression of dorsal markers such as Pax-3 and AL-1; and to the formation of ectopic dorsal clusters of dopaminergic and serotonergic neurons. These findings demonstrate that GLI-1 can reproduce the cell patterning actions of Shh in the developing nervous system and provide support for the hypothesis that it is a mediator of the Shh signal in vertebrates.