Interactions between Sox10, Edn3 and Ednrb during enteric nervous system and melanocyte development
Interactions between Sox10, Edn3 and Ednrb during enteric nervous system and melanocyte development
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DOI：
10.1016/j.ydbio.2006.03.031
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发表时间：
2006-07-01
影响因子：
2.7
通讯作者：
Bondurand, Nadege
中科院分区：
文献类型：
--
作者：
Stanchina, Laure;Baral, Viviane;Bondurand, Nadege
Sox10和ET-3/EDNRB信号通路在肠道神经系统(ENS)和黑素细胞发育过程中的需求，以及它们在Waardenburg-Hirschsprung病(色素沉着减少、耳聋和肠神经节缺失)中的变化已经得到很好的证实。在这里，我们分析了在ENS和黑素细胞发育过程中这些基因之间的遗传相互作用。通过对Sox10；EDNRB和Sox10；Edn3双突变体的表型分析，我们表明这些分子之间的协调和平衡相互作用是正常ENS和黑素细胞发育所必需的。事实上，双重突变体出现了严重的白色斑点增加，内耳内没有黑素细胞，特别是血管纹，以及更严重的ENS缺陷。此外，我们还发现，在Sox10杂合子小鼠中，EDNRB的部分缺失会在观察到的所有阶段损害肠道脊细胞对肠道的定植。然而，与单一突变体相比，我们在胃内的神经脊细胞中没有检测到细胞凋亡、细胞增殖或整体神经元或神经胶质分化缺陷，而在肠道外的迷走神经脊细胞中检测到凋亡增加。这些数据将有助于理解ENS的分子基础，在小鼠突变和携带Sox10、EDN3和EDNRB突变的患者中观察到色素沉着和加热缺陷。(C)2006 Elsevier Inc.保留所有权利。
The requirement for SOX10 and endothelin-3/EDNRB signalling pathway during enteric nervous system (ENS) and melanocyte development, as well as their alterations in Waardenburg-Hirschsprung disease (hypopigmentation, deafness and absence of enteric ganglia) are well established. Here, we analysed the genetic interactions between these genes during ENS and melanocyte development. Through phenotype analysis of Sox10;Ednrb and Sox10;Edn3 double mutants, we show that a coordinate and balanced interaction between these molecules is required for normal ENS and melanocyte development. Indeed, double mutants present with a severe increase in white spotting, absence of melanocytes within the inner ear, and in the stria vascularis in particular, and more severe ENS defects. Moreover, we show that partial loss of Ednrb in Sox10 heterozygous mice impairs colonisation of the gut by enteric crest cells at all stages observed. However, compared to single mutants, we detected no apoptosis, cell proliferation or overall neuronal or glial differentiation defects in neural crest cells within the stomach of double mutants, but apoptosis was increased in vagal neural crest cells outside of the gut. These data will contribute to the understanding of the molecular basis of ENS, pigmentation and heating defects observed in mouse mutants and patients carrying SOX10, EDN3 and EDNRB mutations. (c) 2006 Elsevier Inc. All rights reserved.