Gdnf is mitogenic, neurotrophic, and chemoattractive to enteric neural crest cells in the embryonic colon.
Gdnf is mitogenic, neurotrophic, and chemoattractive to enteric neural crest cells in the embryonic colon.
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Gdnf 对胚胎结肠中的肠神经嵴细胞具有促有丝分裂、神经营养和化学吸引力。
DOI：
10.1002/dvdy.22630
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Goldstein,AllanM
中科院分区：
文献类型：
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作者：
Mwizerwa,Olive;Das,Pragnya;Nagy,Nandor;Akbareian,SophiaE;Mably,JohnD;Goldstein,AllanM
胶质源性神经营养因子（Gdnf）是肠神经系统（ENS）形态发生所必需的，并且已显示其调节培养的肠神经嵴源性细胞（ENCC）的增殖、分化和存活。本研究的目的是研究其在结肠中的体内作用，结肠是最常受肠神经病变如先天性巨结肠影响的部位。通过靶向逆转录病毒介导的基因过表达和基于逆转录病毒载体的基因沉默，在禽类胚胎远端肠道的卵内调节Gdnf活性。我们发现，GDNF对结肠ENCC具有多效性作用，促进增殖，诱导神经元分化，并作为一种化学引诱物。下调GDNF类似地诱导神经元过早分化，但也抑制ENCC增殖，导致远端结直肠无神经节细胞症伴严重的近端神经节细胞减少症。这些结果表明GDNF信号传导在结肠ENS形成中的重要作用，并强调了发育中的ENS中增殖和分化之间的关键平衡。Developmental Dynamics 240：1402-1411，2011。© 2011 Wiley利斯公司
Glial‐derived neurotrophic factor (Gdnf) is required for morphogenesis of the enteric nervous system (ENS) and it has been shown to regulate proliferation, differentiation, and survival of cultured enteric neural crest–derived cells (ENCCs). The goal of this study was to investigate its in vivo role in the colon, the site most commonly affected by intestinal neuropathies such as Hirschsprung's disease. Gdnf activity was modulated in ovo in the distal gut of avian embryos using targeted retrovirus‐mediated gene overexpression and retroviral vector‐based gene silencing. We find that Gdnf has a pleiotropic effect on colonic ENCCs, promoting proliferation, inducing neuronal differentiation, and acting as a chemoattractant. Down‐regulating Gdnf similarly induces premature neuronal differentiation, but also inhibits ENCC proliferation, leading to distal colorectal aganglionosis with severe proximal hypoganglionosis. These results indicate an important role for Gdnf signaling in colonic ENS formation and emphasize the critical balance between proliferation and differentiation in the developing ENS. Developmental Dynamics 240:1402–1411, 2011. © 2011 Wiley‐Liss, Inc.