Regulation of epithelial migration by Scribble in development and wound repair

我们体内上皮细胞（在暴露的身体表面形成薄保护层的细胞，如皮肤和内部腔、导管和器官的内衬）的运动对我们正常的胚胎发育以及受伤后伤口的愈合至关重要。因此，了解这种运动是如何被调节的是医学生物学的一个基本领域。尽管我们对细胞运动的机制了解甚多，但在胚胎发育过程中，或在受伤后，用于协调细胞运动以确保每个细胞迁移到正确位置的信号还不太清楚。许多证据表明，我们体内细胞正确定向所需的蛋白质（细胞的一种特性，称为极性）可能对这一过程至关重要。极性蛋白Scribble在果蝇、斑马鱼和小鼠胚胎发育过程中发生突变，导致上皮组织紊乱。我们现在已经证明，Scribble是细胞正确定位所必需的，以便能够在组织培养和小鼠胚胎发育和伤口愈合过程中对伤口做出反应。目前还不清楚Scribble是如何管理移民的。在这里，我们提出确定Scribble调节的分子，以协调细胞运动在发育和组织修复。这些研究将为细胞运动如何协调的基本过程提供新的见解，并可能导致改进组织损伤治疗的新策略。

The movement of epithelial cells within our body (the cells that form the thin protective layer on exposed bodily surfaces such as skin and the lining of internal cavities, ducts, and organs) is essential for our normal embryonic development as well as for healing of wounds following injury. Understanding how this movement is regulated is therefore a fundamental area of medical biology. Although much is known about the mechanics of how a cell moves, the signals used to coordinate this movement so as to ensure that each cell migrates to the right place during embryonic development or in response to a wound is not well understood. A number of lines of evidence suggest that proteins required for the correct orientation of cells within our body (a property of cells known as polarity) may be essential for this process. Mutation of the polarity protein Scribble in the fly, zebrafish and mouse causes a disorganization of epithelial tissues during embryonic development. We have now shown that Scribble is required for cells to orientate correctly so as to be able to move in response to a wound in tissue culture and also during embryonic development and wound healing in the mouse. It is currently unknown how Scribble regulates migration. Here we propose to identify the molecules that Scribble regulates to coordinate cell movement during development and tissue repair. These studies will provide new insights into the fundamental process of how cell movement is coordinated and could lead to novel strategies for improved treatment of tissue injuries.