Netrins and DCC in the guidance of migrating cells in the developing bowel and neural crest-derived pancreas
Netrins and DCC in the guidance of migrating cells in the developing bowel and neural crest-derived pancreas
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DOI：
10.1016/s0012-1606(03)00136-2
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发表时间：
2003-06-15
影响因子：
2.7
通讯作者：
Gershon, MD
中科院分区：
文献类型：
--
作者：
Jiang, Y;Liu, MT;Gershon, MD
迷走神经嵴衍生的肠神经系统前体通过在肠间质内下降而定植在肠内。垂直的二次迁移，向粘膜和进入胰腺，分别导致粘膜下和胰神经节的形成。我们测试了网络引导这些二次迁移的假设。RT-PCR、原位杂交和免疫细胞化学研究表明，网蛋白（小鼠的网蛋白-1和-3以及小鸡的网蛋白-2）和网蛋白受体[在大肠癌（DCC）、neogenin和腺苷A2b受体中缺失]在胎儿粘膜上皮和胰腺中表达。冠源性细胞表达DCC， DCC受发育调控。crest来源的细胞从肠道外植体向共培养表达netrin-1的细胞或共培养的胰腺外植体迁移。冠源性细胞也向培养的肠环粘膜内迁移。这些迁移被DCC抗体和抑制干扰DCC信号的蛋白激酶A特异性阻断。在缺乏DCC的转基因小鼠中，E12.5、E15和P0时粘膜下和胰神经节缺失。Netrins还促进了肠嵴来源细胞的存活/发育。因此，粘膜下和胰神经节的形成涉及到表达dcc的冠源细胞被网状蛋白吸引。(C) 2003 Elsevier Science（美国）版权所有。
Vagal neural crest-derived precursors of the enteric nervous system colonize the bowel by descending within the enteric mesenchyme. Perpendicular secondary migration, toward the mucosa and into the pancreas, result, respectively, in the formation of submucosal and pancreatic ganglia. We tested the hypothesis that netrins guide these secondary migrations. Studies using RT-PCR, in situ hybridization, and immunocytochemistry indicated that netrins (netrins-1 and -3 mice and netrin-2 in chicks) and netrin receptors [deleted in colorectal cancer (DCC), neogenin, and the adenosine A2b receptor] are expressed by the fetal mucosal epithelium and pancreas. Crest-derived cells expressed DCC, which was developmentally regulated. Crest-derived cells migrated out of explants of gut toward cocultured cells expressing netrin-1 or toward cocultured explants of pancreas. Crest-derived cells also migrated inwardly toward the mucosa of cultured rings of bowel. These migrations were specifically blocked by antibodies to DCC and by inhibition of protein kinase A, which interferes with DCC signaling. Submucosal and pancreatic ganglia were absent at E12.5, E15, and P0 in transgenic mice lacking DCC. Netrins also promoted the survival/development of enteric crest-derived cells. The formation of submucosal and pancreatic ganglia thus involves the attraction of DCC-expressing crest-derived cells by netrins. (C) 2003 Elsevier Science (USA). All rights reserved.