Hedgehog signals regulate multiple aspects of gastrointestinal development.
Hedgehog signals regulate multiple aspects of gastrointestinal development.
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发表时间：
2000-06
期刊：
影响因子：
4.6
通讯作者：
M. Ramalho-Santos;D. Melton;A. McMahon
中科院分区：
文献类型：
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作者：
M. Ramalho-Santos;D. Melton;A. McMahon
胃肠道由胚胎肠发育而来，由内胚层来源的上皮细胞和中胚层来源的细胞组成。这两个组织层之间的细胞信号传导似乎在协调肠道及其衍生物的模式化和器官发生中起着关键作用。我们已经评估了Sonic hedgehog和Indian hedgehog基因的功能，这些基因编码细胞信号的Hedgehog家族成员。两者都在肠内胚层中表达，而靶基因在间充质中的离散层中表达。目前还不清楚这两个基因之间的功能冗余是否会妨碍对小鼠肠道中Hedgehog信号传导作用的遗传分析。我们在这里表明，小鼠肠道既有共同的和单独的要求，音速刺猬和印度刺猬。Sonic hedgehog和Indian hedgehog突变小鼠均显示平滑肌减少、肠旋转不良和环状胰腺。音刺猬突变体显示胃的肠转化、十二指肠狭窄（梗阻）、肠道和肛门的异常神经支配。印度刺猬突变体显示上皮干细胞增殖和分化减少，以及先天性巨结肠（无神经节结肠）的典型特征。这些结果表明，刺猬信号是必不可少的哺乳动物胃肠道的器官形成，并建议在这个信号通路的成员突变可能参与人类胃肠道畸形。
The gastrointestinal tract develops from the embryonic gut, which is composed of an endodermally derived epithelium surrounded by cells of mesodermal origin. Cell signaling between these two tissue layers appears to play a critical role in coordinating patterning and organogenesis of the gut and its derivatives. We have assessed the function of Sonic hedgehog and Indian hedgehog genes, which encode members of the Hedgehog family of cell signals. Both are expressed in gut endoderm, whereas target genes are expressed in discrete layers in the mesenchyme. It was unclear whether functional redundancy between the two genes would preclude a genetic analysis of the roles of Hedgehog signaling in the mouse gut. We show here that the mouse gut has both common and separate requirements for Sonic hedgehog and Indian hedgehog. Both Sonic hedgehog and Indian hedgehog mutant mice show reduced smooth muscle, gut malrotation and annular pancreas. Sonic hedgehog mutants display intestinal transformation of the stomach, duodenal stenosis (obstruction), abnormal innervation of the gut and imperforate anus. Indian hedgehog mutants show reduced epithelial stem cell proliferation and differentiation, together with features typical of Hirschsprung's disease (aganglionic colon). These results show that Hedgehog signals are essential for organogenesis of the mammalian gastrointestinal tract and suggest that mutations in members of this signaling pathway may be involved in human gastrointestinal malformations.