The receptor tyrosine kinase RET regulates hindgut colonization by sacral neural crest cells
The receptor tyrosine kinase RET regulates hindgut colonization by sacral neural crest cells
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DOI：
10.1016/j.ydbio.2007.10.028
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发表时间：
2008-01-01
影响因子：
2.7
通讯作者：
Bums, Alan J.
中科院分区：
文献类型：
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作者：
Delalande, Jean-Marie;Barlow, Amanda J.;Bums, Alan J.
肠神经系统(ENS)由迷走神经和骶神经脊细胞(NCC)组成。迷走神经NCC在整个肠道中起主要作用，而骶部NCC的作用主要局限于后肠。这一点，以及来自异位鹌鹑-雏鸡移植研究的数据，表明迷走神经和骶骨NCC在肠道定植和/或对肠道环境中的信号提示做出反应的能力方面存在内在的差异。为了更好地理解这些差异的分子基础，我们研究了已知对ENS形成至关重要的基因在鸡后肠内的骶骨NCC中的表达。我们的结果表明，与迷走神经NCC一样，Sox10、EDNRB和Ret在肠道内的骶骨NCC中也有表达。由于我们没有检测到这些ENS基因在表达上的质的差异，我们对迷走神经和骶骨NCC进行了DNA微阵列分析。在从总数据集检查的关键ENS基因中，Ret是唯一被鉴定为高度差异表达的基因，迷走神经NCC的表达比骶骨NCC增加了四倍。我们还发现，RET在骶骨NCC中的过度表达增加了其ENS的发育潜能，使更多的细胞在发育早期进入肠道，从而促进了骶骨NCC向迷走神经NCC的命运。(C)2007 Elsevier Inc.保留所有权利。
The enteric nervous system (ENS) is formed from vagal and sacral neural crest cells (NCC). Vagal NCC give rise to most of the ENS along the entire gut, whereas the contribution of sacral NCC is mainly limited to the hindgut. This, and data from heterotopic quail-chick grafting studies, suggests that vagal and sacral NCC have intrinsic differences in their ability to colonize the gut, and/or to respond to signalling cues within the gut environment. To better understand the molecular basis of these differences, we studied the expression of genes known to be essential for ENS formation, in sacral NCC within the chick hindgut. Our results demonstrate that, as in vagal NCC, Sox10, EdnrB, and Ret are expressed in sacral NCC within the gut. Since we did not detect a qualitative difference in expression of these ENS genes we performed DNA microarray analysis of vagal and sacral NCC. Of I I key ENS genes examined from the total data set, Ret was the only gene identified as being highly differentially expressed, with a fourfold increase in expression in vagal versus sacral NCC. We also found that over-expression of RET in sacral NCC increased their ENS developmental potential such that larger numbers of cells entered the gut earlier in development, thus promoting the fate of sacral NCC towards that of vagal NCC. (c) 2007 Elsevier Inc. All rights reserved.