Roles for Nkx2-5 and Gata3 in the ontogeny of the murine smooth muscle gastric ligaments.
Roles for Nkx2-5 and Gata3 in the ontogeny of the murine smooth muscle gastric ligaments.
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DOI：
10.1152/ajpgi.00360.2013
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发表时间：
2014-08
期刊：
影响因子：
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通讯作者：
A. Prakash;A. Udager;David A Saenz;D. Gumucio
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文献类型：
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作者：
A. Prakash;A. Udager;David A Saenz;D. Gumucio
胃韧带是一种浅层索状结构，位于胃的小弯上，从幽门延伸到食道。这些韧带在包括人类在内的多种哺乳动物中都有记录，但它们的组成和个体发育还没有被探索过。在这里，我们证明，在个体发育过程中，胃韧带首先作为GATA3表达细胞的C型结构域的延伸出现在未来的幽门周围；这个结构域稍后将形成幽门外纵肌(OLM)。C的开放端位于腹侧，从胚胎13.5天开始，韧带从这些点向前生长。虽然胃的大多数其他韧带本质上是神经血管的，但胃韧带是由在E14.5到E16.5之间成熟的平滑肌细胞组成的。胃韧带共表达转录因子GATA3、Nkx2-5和Sox9，GATA3的胚系缺失或Nkx2-5的条件性缺失会抑制Sox9的表达并损害胃韧带的平滑肌发育；类似的表型在OLM中也曾见过。根据OLM和胃韧带之间的这种分子邻接性，三维图像重建突出了这些平滑肌结构之间的物理邻接性，表明它们可能作为一个单位共同控制幽门区域的弯曲，这一功能类似于Treitz韧带在十二指肠空肠交界处的功能。这些发现可能对我们理解正常的幽门括约肌功能，以及常见的人类先天性病理特发性肥厚性幽门狭窄有意义。
The gastric ligaments are superficial cord-like structures, located on the lesser curvature of the stomach, that extend from the pylorus to the esophagus. These ligaments have been documented in a wide variety of mammalian species, including humans, but their composition and ontogeny is unexplored. Here, we demonstrate that, during ontogeny, the gastric ligaments are first visible as extensions from a C-shaped domain of Gata3-expressing cells that surround the future pylorus; this domain will later give rise to the pyloric outer longitudinal muscle (OLM). The open ends of the C are located ventrally, and, beginning at embryonic day (E) 13.5, the ligaments grow anteriorly from these points. Whereas most other ligaments of the stomach are neurovascular in nature, the gastric ligaments are composed of smooth muscle cells that mature between E14.5 and E16.5. The gastric ligaments coexpress the transcription factors Gata3, Nkx2-5, and Sox9, and germline loss of Gata3 or conditional deletion of Nkx2-5 abrogates Sox9 expression and impairs gastric ligament smooth muscle development; similar phenotypes were previously seen in the OLM. In accord with this molecular contiguity between the OLM and gastric ligaments, three-dimensional image reconstruction highlights physical contiguity between these smooth muscle structures, suggesting that they may work together as a unit to control flexure of the pyloric region, a function similar to the ligament of Treitz at the duodenojejunal junction. These findings may have implications for our understanding of normal pyloric sphincter function, as well as the common human congenital pathology idiopathic hypertrophic pyloric stenosis.