Regulation of Patched by Sonic hedgehog in the developing neural tube
Regulation of Patched by Sonic hedgehog in the developing neural tube
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DOI：
10.1073/pnas.93.18.9346
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发表时间：
1996-09-03
影响因子：
11.1
通讯作者：
Tabin, CJ
中科院分区：
文献类型：
--
作者：
Marigo, V;Tabin, CJ
Sonic hedgehog是果蝇分泌的hedgehog蛋白的同源物，在中枢神经系统中诱导神经细胞的命运。Sonic hedgehog已被鉴定为信号诱导底板、运动神经元和多巴胺能神经元。Sonic hedgehog也参与了体节发育中腹侧细胞类型的诱导，ptc是果蝇hedgehog信号通路中的关键基因，参与了hedgehog信号的转导，也是该信号的转录靶点。PTC是果蝇基因的脊椎动物同源物，在肢芽中位于Sonic hedgehog（Shh）的基因下游。我们分析了PTC在鸡神经酸体节发育过程中的表达，发现它在这些组织的所有区域中表达，这些区域已知对Sonic hedgehog信号有反应。在肢芽中，Sonic hedgehog的异位表达导致PTC在神经管和近轴中胚层中的异位诱导。这种调节的保守性允许我们使用PTC作为Sonic hedgehog反应的标记。PTC的表达模式表明，Sonic hedgehog可能在神经管的更多背侧区域中发挥诱导作用。对PTC表达模式的研究还表明，PTC可能在负反馈回路中起作用，以减弱hedgehog信号传导。
Ventral cell fates in the central nervous system are induced by Sonic hedgehog, a homolog of hedgehog, a secreted Drosophila protein, In the central nervous system. Sonic hedgehog has been identified as the signal inducing floor plate, motor neurons, and dopaminergic neurons. Sonic hedgehog is also involved in the induction of ventral cell type in the developing somites, ptc is a key gene in the Drosophila hedgehog signaling pathway where it is involved in transducing the hedgehog signal and is also a transcriptional target of the signal. PTC, a vertebrate homolog of this Drosophila gene, is genetically downstream of Sonic hedgehog (Shh) in the limb bud. We analyze PTC expression during chicken neural acid somite development and find it expressed in all regions of these tissues known to be responsive to Sonic hedgehog signal. As in the limb bud, ectopic expression of Sonic hedgehog leads to ectopic induction of PTC in the neural tube and paraxial mesoderm. This conservation of regulation allows us to use PTC as a marker for Sonic hedgehog response. The pattern of PTC expression suggests that Sonic hedgehog may play an inductive role in more dorsal regions of the neural tube than have been previously demonstrated. Examination of the pattern of PTC expression also suggests that PTC may act in a negative feedback loop to attenuate hedgehog signaling.