Maintenance of mammalian enteric nervous system progenitors by SOX10 and endothelin 3 signalling.

IF 3.7 2区 生物学 Q1 DEVELOPMENTAL BIOLOGY
Development Pub Date : 2006-05-01 Epub Date: 2006-04-19 DOI:10.1242/dev.02375
Nadege Bondurand, Dipa Natarajan, Amanda Barlow, Nikhil Thapar, Vassilis Pachnis
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引用次数: 155

Abstract

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.

SOX10和内皮素3信号传导对哺乳动物肠神经系统祖细胞的维持作用。
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)的发育中起重要作用。通过克隆细胞培养系统,我们发现SOX10抑制多系ENS祖细胞(EPCs)的明显神经元和胶质分化,而不干扰其神经源性承诺。我们还证明,内皮素3可逆地抑制EPCs沿神经源性和胶质源性谱系的承诺和分化,表明该因子在维持多谱系ENS祖细胞中的作用。与这种作用相一致的是,在内皮素3缺陷胚胎的肠道中,表达sox10的祖细胞在肠道神经嵴细胞总数中的比例降低。这种减少可能与内皮素信号传导对ENS祖细胞增殖的要求有关。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有关。我们的研究结果表明,SOX10和内皮素3在维持多系肠神经系统祖细胞中起着至关重要的作用。
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来源期刊
Development
Development 生物-发育生物学
CiteScore
6.70
自引率
4.30%
发文量
433
审稿时长
3 months
期刊介绍: Development’s scope covers all aspects of plant and animal development, including stem cell biology and regeneration. The single most important criterion for acceptance in Development is scientific excellence. Research papers (articles and reports) should therefore pose and test a significant hypothesis or address a significant question, and should provide novel perspectives that advance our understanding of development. We also encourage submission of papers that use computational methods or mathematical models to obtain significant new insights into developmental biology topics. Manuscripts that are descriptive in nature will be considered only when they lay important groundwork for a field and/or provide novel resources for understanding developmental processes of broad interest to the community. Development includes a Techniques and Resources section for the publication of new methods, datasets, and other types of resources. Papers describing new techniques should include a proof-of-principle demonstration that the technique is valuable to the developmental biology community; they need not include in-depth follow-up analysis. The technique must be described in sufficient detail to be easily replicated by other investigators. Development will also consider protocol-type papers of exceptional interest to the community. We welcome submission of Resource papers, for example those reporting new databases, systems-level datasets, or genetic resources of major value to the developmental biology community. For all papers, the data or resource described must be made available to the community with minimal restrictions upon publication. To aid navigability, Development has dedicated sections of the journal to stem cells & regeneration and to human development. The criteria for acceptance into these sections is identical to those outlined above. Authors and editors are encouraged to nominate appropriate manuscripts for inclusion in one of these sections.
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