Gli2 is required for induction of floor plate and adjacent cells, but not most ventral neurons in the mouse central nervous system.
Gli2 is required for induction of floor plate and adjacent cells, but not most ventral neurons in the mouse central nervous system.
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发表时间：
1998-08
期刊：
影响因子：
4.6
通讯作者：
M. Matise;D. Epstein;Heidi L. Park;K. Platt;A. Joyner
中科院分区：
文献类型：
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作者：
M. Matise;D. Epstein;Heidi L. Park;K. Platt;A. Joyner
在脊椎动物中枢神经系统（CNS）中，在神经管的腹侧中线处诱导底板是建立背腹（d/v）极性的最早事件之一。分泌的分子Sonic hedgehog已被证明是这种诱导的必要和充分条件。在脊椎动物中，已经鉴定了该信号通路的几个下游组分，包括Gli转录因子家族的成员。在这项研究中，我们研究了d/v模式的中枢神经系统Gli 2小鼠突变体。我们已经发现，整个中脑，后脑和脊髓的底板不形成Gli 2纯合子。尽管如此，运动神经元和腹侧中间神经元的形成在其正常的d/v位置在9.5至12.5天postcocholation（dpc）。然而，在底板两侧区域产生的细胞，包括多巴胺能和多巴胺能神经元，在Gli 2纯合子胚胎中数量大大减少或不存在。这些结果表明，来自脊索的早期信号可以足以建立腹侧脊髓和后脑细胞分化的基本d/v域。有趣的是，Gli 2突变体中的脊索在10.5 dpc后不像正常胚胎那样向腹侧退化。最后，脊髓的Gli 1/Gli 2锌指缺失双纯合子突变体出现类似Gli 2纯合子，这表明，无论是基因是必需的下游Shh的腹侧细胞的命运腹侧中线外的早期发展。
Induction of the floor plate at the ventral midline of the neural tube is one of the earliest events in the establishment of dorsoventral (d/v) polarity in the vertebrate central nervous system (CNS). The secreted molecule, Sonic hedgehog, has been shown to be both necessary and sufficient for this induction. In vertebrates, several downstream components of this signalling pathway have been identified, including members of the Gli transcription factor family. In this study, we have examined d/v patterning of the CNS in Gli2 mouse mutants. We have found that the floor plate throughout the midbrain, hindbrain and spinal cord does not form in Gli2 homozygotes. Despite this, motoneurons and ventral interneurons form in their normal d/v positions at 9.5 to 12.5 days postcoitum (dpc). However, cells that are generated in the region flanking the floor plate, including dopaminergic and serotonergic neurons, were greatly reduced in number or absent in Gli2 homozygous embryos. These results suggest that early signals derived from the notochord can be sufficient for establishing the basic d/v domains of cell differentiation in the ventral spinal cord and hindbrain. Interestingly, the notochord in Gli2 mutants does not regress ventrally after 10.5 dpc, as in normal embryos. Finally, the spinal cord of Gli1/Gli2 zinc-finger-deletion double homozygous mutants appeared similar to Gli2 homozygotes, indicating that neither gene is required downstream of Shh for the early development of ventral cell fates outside the ventral midline.