Enabled plays key roles in embryonic epithelial morphogenesis in Drosophila
Enabled plays key roles in embryonic epithelial morphogenesis in Drosophila
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DOI：
10.1242/dev.02849
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发表时间：
2007-06-01
期刊：
影响因子：
4.6
通讯作者：
Peifer, Mark
中科院分区：
文献类型：
--
作者：
Gates, Julie;Mahaffey, James P.;Peifer, Mark
在培养细胞和体外研究已经确定了许多肌动蛋白调节剂，并开始确定其作用机制。其中包括使能（Ena）/VASP蛋白、影响成纤维细胞迁移、生长锥运动性和体外角质形成细胞粘附的抗加帽蛋白。然而，部分冗余的家庭成员在哺乳动物和孕产妇Ena果蝇的贡献，以前阻止评估的ENA/VASP蛋白在胚胎形态发生在苍蝇或哺乳动物的作用。我们使用了几种方法来去除母体和合子Ena功能，使我们能够解决这个问题。我们发现灭活Ena不会破坏细胞粘附或上皮组织，这表明它在这些过程中的作用是细胞类型特异性的。然而，Ena在许多形态发生事件中起着重要作用，包括胚带收缩、节沟收缩和头部内卷，而在其他形态发生运动中则是次要的。我们专注于背侧闭合，分析Ena的作用机制。Ena调节丝状伪足的数量和长度，从而影响上皮拉链的速度和细胞与正确邻居匹配的能力。我们还探讨了丝状伪足调控培养果蝇细胞和胚胎。这些数据提供了新的见解，这一重要的肌动蛋白调节器的发展和机制的作用。
Studies in cultured cells and in vitro have identified many actin regulators and begun to define their mechanisms of action. Among these are Enabled ( Ena)/VASP proteins, anti-Capping proteins that influence fibroblast migration, growth cone motility, and keratinocyte cell adhesion in vitro. However, partially redundant family members in mammals and maternal Ena contribution in Drosophila previously prevented assessment of the roles of Ena/VASP proteins in embryonic morphogenesis in flies or mammals. We used several approaches to remove maternal and zygotic Ena function, allowing us to address this question. We found that inactivating Ena does not disrupt cell adhesion or epithelial organization, suggesting its role in these processes is cell type-specific. However, Ena plays an important role in many morphogenetic events, including germband retraction, segmental groove retraction and head involution, whereas it is dispensable for other morphogenetic movements. We focused on dorsal closure, analyzing mechanisms by which Ena acts. Ena modulates filopodial number and length, thus influencing the speed of epithelial zippering and the ability of cells to match with correct neighbors. We also explored filopodial regulation in cultured Drosophila cells and embryos. These data provide new insights into developmental and mechanistic roles of this important actin regulator.