Sonic hedgehog regulates the proliferation, differentiation, and migration of enteric neural crest cells in gut.

Sonic hedgehog regulates the proliferation, differentiation, and migration of enteric neural crest cells in gut.
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DOI:
10.1083/jcb.200401077
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发表时间:
2004-08-30
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Tam PK
Tam PK
中科院分区:
其他
文献类型:
--
作者:
Fu M;Lui VC;Sham MH;Pachnis V;Tam PK

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在脊椎动物胚胎中,肠神经脊细胞(NCC)迁移和定植于整个肠道,并增殖和分化为肠神经系统的神经元和神经胶质细胞。我们研究了Sonic Hedgehog(Shh)在细胞和器官培养中对肠道NCCs的促有丝分裂和形态发生作用。肠源性NCC表达Shh受体补丁和编码Shh信号转导蛋白(Gli1)的转录本。Shh促进神经干细胞的增殖,抑制其分化。胶质细胞源性神经营养因子(GDNF)对NCCs的促神经生成作用可被Shh所消除。在肠道外植体中,如果添加GDNF,NCC从外植体迁移到相邻的基质上,而添加Shh则取消了这种迁移。外植体中神经嵴来源的细胞向肌间神经丛的分化和融合受到抑制。我们的数据提示Shh控制NCC的增殖和分化,并调节NCC对GDNF诱导的反应性。
Enteric neural crest cells (NCCs) migrate and colonize the entire gut and proliferate and differentiate into neurons and glia of the enteric nervous system in vertebrate embryos. We have investigated the mitogenic and morphogenic functions of Sonic hedgehog (Shh) on enteric NCCs in cell and organ culture. Enteric NCCs expressed Shh receptor Patched and transcripts encoding the Shh signal transducer (Gli1). Shh promoted the proliferation and inhibited the differentiation of NCCs. The pro-neurogenic effect of glial cell line–derived neurotrophic factor (GDNF) on NCCs was abolished by Shh. In gut explants, NCCs migrated from the explants onto the adjacent substratum if GDNF was added, whereas addition of Shh abolished this migration. Neuronal differentiation and coalescence of neural crest–derived cells into myenteric plexuses in explants was repressed by the addition of Shh. Our data suggest that Shh controls the proliferation and differentiation of NCCs and modulates the responsiveness of NCCs toward GDNF inductions.
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