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音猬因子在发育中的神经管中对帕奇蛋白的调控。

Regulation of patched by sonic hedgehog in the developing neural tube.

作者信息

Marigo V, Tabin C J

机构信息

Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

出版信息

Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9346-51. doi: 10.1073/pnas.93.18.9346.

Abstract

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 and 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.

摘要

中枢神经系统中的腹侧细胞命运是由音猬因子诱导的,音猬因子是刺猬因子的同源物,而刺猬因子是一种果蝇分泌蛋白。在中枢神经系统中,音猬因子已被确定为诱导底板、运动神经元和多巴胺能神经元的信号。音猬因子还参与发育中的体节腹侧细胞类型的诱导。patched(ptc)基因是果蝇刺猬信号通路中的关键基因,它参与传递刺猬信号,也是该信号的转录靶点。PTC是这个果蝇基因的脊椎动物同源物,在肢芽中位于音猬因子(Shh)的遗传下游。我们分析了鸡神经和体节发育过程中PTC的表达情况,发现它在这些组织中所有已知对音猬因子信号有反应的区域都有表达。与在肢芽中一样,音猬因子的异位表达会导致神经管和轴旁中胚层中PTC的异位诱导。这种调控的保守性使我们能够将PTC用作音猬因子反应的标记物。PTC的表达模式表明,音猬因子可能在神经管比以前证明的更靠背侧的区域发挥诱导作用。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,以减弱刺猬信号。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edc8/38430/0add2afc9d09/pnas01522-0058-a.jpg

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