Smooth muscle fascicular reorientation is required for esophageal morphogenesis and dependent on Cdo.
Smooth muscle fascicular reorientation is required for esophageal morphogenesis and dependent on Cdo.
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DOI：
10.1083/jcb.201301005
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发表时间：
2013-04-15
期刊：
影响因子：
--
通讯作者：
Krauss RS
中科院分区：
文献类型：
--
作者：
Romer AI;Singh J;Rattan S;Krauss RS
cdo缺陷小鼠在食管形态发生过程中平滑肌束重定向缺陷，导致结构和功能缺陷，包括近端骨-平滑肌边界异常和失弛缓症。出生后食管肌肉的成熟涉及近端到远端平滑肌与骨骼肌的替代，其机制难以捉摸。我们报道了这一过程在缺乏细胞表面受体Cdo的小鼠中受损，并确定了潜在的发育机制。含有增生性骨骼肌前体细胞的成肌过渡区沿近端到远端方向迁移，留下分化的肌纤维。在过渡区的远端，平滑肌束经历了一个形态发生过程，在此过程中，它们相对于彼此和相对于管腔改变了方向。因此，为过渡区开辟了一条通道，平滑肌最终只占据了最远端的食道；没有平滑肌萎缩。Cdo - / -小鼠在肌束重定向方面存在特异性缺陷，导致骨-平滑肌近端边界异常。此外，Cdo - / -小鼠表现出食管肥大和贲门失弛缓，它们的下食管括约肌对一氧化氮诱导的松弛具有抗性，这表明模式和括约肌功能之间存在发育联系。总的来说，这些结果阐明了食管形态发生和运动障碍的机制。
Cdo-deficient mice have defects in smooth muscle fascicular reorientation during esophageal morphogenesis, resulting in structural and functional defects including an aberrantly proximal skeletal–smooth muscle boundary and achalasia. Postnatal maturation of esophageal musculature involves proximal-to-distal replacement of smooth muscle with skeletal muscle by elusive mechanisms. We report that this process is impaired in mice lacking the cell surface receptor Cdo and identify the underlying developmental mechanism. A myogenic transition zone containing proliferative skeletal muscle precursor cells migrated in a proximal–distal direction, leaving differentiated myofibers in its wake. Distal to the transition zone, smooth muscle fascicles underwent a morphogenetic process whereby they changed their orientation relative to each other and to the lumen. Consequently, a path was cleared for the transition zone, and smooth muscle ultimately occupied only the distal-most esophagus; there was no loss of smooth muscle. Cdo−/− mice were specifically defective in fascicular reorientation, resulting in an aberrantly proximal skeletal–smooth muscle boundary. Furthermore, Cdo−/− mice displayed megaesophagus and achalasia, and their lower esophageal sphincter was resistant to nitric oxide–induced relaxation, suggesting a developmental linkage between patterning and sphincter function. Collectively, these results illuminate mechanisms of esophageal morphogenesis and motility disorders.
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