Enteric neural crest-derived cells promote their migration by modifying their microenvironment through tenascin-C production.

Enteric neural crest-derived cells promote their migration by modifying their microenvironment through tenascin-C production.
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DOI:
10.1016/j.ydbio.2013.08.006
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发表时间:
2013-10-15
影响因子:
2.7
通讯作者:
Goldstein, Allan M.
Goldstein, Allan M.
中科院分区:
生物学3区
文献类型:
--
作者:
Akbareian, Sophia E.;Nagy, Nandor;Steiger, Casey E.;Mably, John D.;Miller, Sarah A.;Hotta, Ryo;Molnar, David;Goldstein, Allan M.

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肠神经系统 (ENS) 源自迷走神经和骶神经嵴细胞,这些细胞在肠壁内迁移、增殖并分化为肠神经元和神经胶质细胞。尽管肠神经嵴衍生细胞(ENCC)迁移的过程在肠道形成和功能中很重要,但其调节机制尚不清楚。 ENCC 迁移相关基因的表征对于理解 ENS 的发展至关重要,并且可以为人类 ENS 疾病的治疗提供靶标。我们确定细胞外基质糖蛋白腱蛋白-C (TNC) 是 ENCC 发育的重要调节因子。我们发现 TNC 在禽类肠道发育过程中动态表达。在 ENCC 到达之前,它在盲肠区域不存在,但当 ENCC 进入盲肠和后肠时,它在 ENCC 周围强烈表达。在无神经节后肠中,TNC 表达在整个外间充质中很强,但在粘膜下区域不存在,这支持了肠壁内 ENCC 依赖性和独立表达的存在。使用大鼠雏鸡体腔移植物、神经管培养物和肠道外植体,我们发现 ENCC 产生 TNC,并且这种 ECM 蛋白促进它们的迁移。有趣的是,只有迷走神经嵴衍生的 ENCC 表达 TNC,而骶神经嵴衍生的细胞则不表达 TNC。这些结果表明,迷走神经嵴衍生的 ENCC 通过 TNC 表达主动改变其微环境,从而有助于调节其自身的迁移。
The enteric nervous system (ENS) is derived from vagal and sacral neural crest cells that migrate, proliferate, and differentiate into enteric neurons and glia within the gut wall. The mechanisms regulating enteric neural crest-derived cell (ENCC) migration are poorly characterized despite the importance of this process in gut formation and function. Characterization of genes involved in ENCC migration is essential to understanding ENS development and could provide targets for treatment of human ENS disorders. We identified the extracellular matrix glycoprotein tenascin-C (TNC) as an important regulator of ENCC development. We find TNC dynamically expressed during avian gut development. It is absent from the cecal region just prior to ENCC arrival, but becomes strongly expressed around ENCCs as they enter the ceca and hindgut. In aganglionic hindguts, TNC expression is strong throughout the outer mesenchyme, but is absent from the submucosal region, supporting the presence of both ENCC-dependent and independent expression within the gut wall. Using rat-chick coelomic grafts, neural tube cultures, and gut explants, we show that ENCCs produce TNC and that this ECM protein promotes their migration. Interestingly, only vagal neural crest-derived ENCCs express TNC, whereas sacral neural crest-derived cells do not. These results demonstrate that vagal crest-derived ENCCs actively modify their microenvironment through TNC expression and thereby help to regulate their own migration.
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