Cell Biology Section, Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
Dev Dyn. 2013 Sep;242(9):1066-77. doi: 10.1002/dvdy.24000. Epub 2013 Aug 12.
Epithelial cells of developing embryonic organs, such as salivary glands, can display substantial motility during branching morphogenesis. Their dynamic movements and molecules involved in their migration are not fully characterized.
We generated transgenic mice expressing photo-convertible KikGR and tracked the movements of individual cells highlighted by red fluorescence in different regions of developing salivary glands. Motility was highest for outer bud epithelial cells adjacent to the basement membrane, lower in inner bud cells, and lowest in duct cells. The highly motile outer cells contacting the basement membrane were pleomorphic, whereas inner cells were rounded. Peripheral cell motility was disrupted by antibodies inhibiting α6+β1 integrins and the nonmuscle myosin II inhibitor blebbistatin. Inner bud cell migration was unaffected by these inhibitors, but their rate of migration was stimulated by inhibiting E-cadherin.
Cell motility in developing salivary glands was highest in cells in contact with the basement membrane. The basement membrane-associated motility of these outer bud cells depended on integrins and myosin II, but not E-cadherin. In contrast, motility of inner bud cells was restrained by E-cadherin. These findings identify the importance of integrin-dependent basement membrane association for the morphology, tissue organization, and lateral motility of morphogenetic epithelial cells.
在分支形态发生过程中，发育中胚胎器官（如唾液腺）的上皮细胞可以表现出很大的运动性。它们的动态运动及其迁移所涉及的分子尚未完全表征。
我们生成了表达光转化 KikGR 的转基因小鼠，并跟踪了不同发育中的唾液腺区域中用红色荧光标记的单个细胞的运动。靠近基膜的外芽上皮细胞的运动性最高，内芽细胞的运动性较低，导管细胞的运动性最低。与基膜接触的高迁移性外细胞呈多形性，而内细胞呈圆形。用抑制α6+β1 整合素和非肌肉肌球蛋白 II 抑制剂 blebbistatin 的抗体破坏外围细胞的迁移。这些抑制剂对内芽细胞的迁移没有影响，但抑制 E-钙粘蛋白会刺激其迁移率。
在发育中的唾液腺中，细胞迁移性在与基膜接触的细胞中最高。这些外芽细胞与基膜相关的运动依赖于整合素和肌球蛋白 II，但不依赖于 E-钙粘蛋白。相比之下，内芽细胞的运动性受到 E-钙粘蛋白的限制。这些发现表明，整合素依赖性基膜附着对于形态发生上皮细胞的形态、组织组织和侧向运动性很重要。
