Localized Smooth Muscle Differentiation Is Essential for Epithelial Bifurcation during Branching Morphogenesis of the Mammalian Lung.
Localized Smooth Muscle Differentiation Is Essential for Epithelial Bifurcation during Branching Morphogenesis of the Mammalian Lung.
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DOI：
10.1016/j.devcel.2015.08.012
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发表时间：
2015-09-28
影响因子：
11.8
通讯作者：
Nelson CM
中科院分区：
文献类型：
--
作者：
Kim HY;Pang MF;Varner VD;Kojima L;Miller E;Radisky DC;Nelson CM
气道上皮通过分支形态发生发育成树状结构。在这里，我们显示了一个关键的作用，在胚胎小鼠肺上皮分叉气道平滑肌的局部分化。我们发现，在终端分叉，在新生芽的几何形状的变化与图案平滑肌分化相吻合。在报告小鼠中评估α-平滑肌肌动蛋白（αSMA）的时空动力学发现，α SMA表达细胞在分叉前出现在未来上皮裂隙的基底表面，然后随着它们缠绕分叉芽而密度增加。破坏这种定型的平滑肌分化模式可以防止终末分叉。我们的研究结果揭示了定型分化的气道平滑肌相邻的新生上皮芽，并建议，本地化的平滑肌包裹在裂缝网站所需的终端分叉在气道分支形态发生。
The airway epithelium develops into a treelike structure via branching morphogenesis. Here we show a critical role for localized differentiation of airway smooth muscle during epithelial bifurcation in the embryonic mouse lung. We found that during terminal bifurcation, changes in the geometry of nascent buds coincided with patterned smooth muscle differentiation. Evaluating spatiotemporal dynamics of α-smooth muscle actin (αSMA) in reporter mice revealed that αSMA-expressing cells appear at the basal surface of the future epithelial cleft prior to bifurcation, and then increase in density as they wrap around the bifurcating bud. Disrupting this stereotyped pattern of smooth muscle differentiation prevents terminal bifurcation. Our results reveal stereotyped differentiation of airway smooth muscle adjacent to nascent epithelial buds and suggest that localized smooth muscle wrapping at the cleft site is required for terminal bifurcation during airway branching morphogenesis.