Fu Ming, Lui Vincent Chi Hang, Sham Mai Har, Pachnis Vassilis, Tam Paul Kwong Hang
Department of Surgery, The University of Hong Kong, 21 Sassoon Rd., Pokfulam, Hong Kong, HKSAR China.
J Cell Biol. 2004 Aug 30;166(5):673-84. doi: 10.1083/jcb.200401077.
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.
在脊椎动物胚胎中，肠神经嵴细胞（NCCs）迁移并定植于整个肠道，增殖并分化为肠神经系统的神经元和神经胶质细胞。我们在细胞和器官培养中研究了音猬因子（Shh）对肠NCCs的促有丝分裂和形态发生功能。肠NCCs表达Shh受体Patched以及编码Shh信号转导蛋白（Gli1）的转录本。Shh促进NCCs的增殖并抑制其分化。Shh消除了胶质细胞系源性神经营养因子（GDNF）对NCCs的促神经生成作用。在肠道外植体中，如果添加GDNF，NCCs会从外植体迁移到相邻基质上，而添加Shh则会消除这种迁移。添加Shh会抑制外植体中神经嵴衍生细胞的神经元分化以及它们聚集成肌间神经丛。我们的数据表明，Shh控制NCCs的增殖和分化，并调节NCCs对GDNF诱导的反应性。
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