Bondurand Nadege, Natarajan Dipa, Barlow Amanda, Thapar Nikhil, Pachnis Vassilis
Division of Molecular Neurobiology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Development. 2006 May;133(10):2075-86. doi: 10.1242/dev.02375. Epub 2006 Apr 19.
The transcriptional regulator SOX10 and the signalling molecule endothelin 3 have important roles in the development of the mammalian enteric nervous system (ENS). Using a clonal cell culture system, we show that SOX10 inhibits overt neuronal and glial differentiation of multilineage ENS progenitor cells (EPCs), without interfering with their neurogenic commitment. We also demonstrate that endothelin 3 inhibits reversibly the commitment and differentiation of EPCs along the neurogenic and gliogenic lineages, suggesting a role for this factor in the maintenance of multilineage ENS progenitors. Consistent with such a role, the proportion of Sox10-expressing progenitors in the total population of enteric neural crest cells is reduced in the gut of endothelin 3-deficient embryos. This reduction may be related to the requirement of endothelin signalling for the proliferation of ENS progenitors. The dependence of ENS progenitors on endothelin 3 is more pronounced at the migratory front of enteric neural crest cells, which is associated with relatively high levels of endothelin 3 mRNA. Our findings indicate that SOX10 and endothelin 3 have a crucial role in the maintenance of multilineage enteric nervous system progenitors.
转录调节因子SOX10和信号分子内皮素3在哺乳动物肠神经系统（ENS）的发育中发挥着重要作用。利用克隆细胞培养系统，我们发现SOX10可抑制多谱系ENS祖细胞（EPC）向神经元和神经胶质细胞的明显分化，而不干扰其神经发生的定向分化。我们还证明，内皮素3可可逆地抑制EPC沿神经发生和胶质发生谱系的定向分化和分化，这表明该因子在维持多谱系ENS祖细胞中发挥作用。与此作用一致，在内皮素3缺陷胚胎的肠道中，肠神经嵴细胞总数中表达Sox10的祖细胞比例降低。这种降低可能与内皮素信号传导对ENS祖细胞增殖的需求有关。ENS祖细胞对内皮素3的依赖性在肠神经嵴细胞的迁移前沿更为明显，这与相对高水平的内皮素3 mRNA相关。我们的研究结果表明，SOX10和内皮素3在维持多谱系肠神经系统祖细胞中起着关键作用。
