ECM, integrins, and action in salivary morphogenesis

描述：(申请人提供)分支形态发生是一个复杂的过程 在唾液腺、肺、肾发育过程中发生的过程， 前列腺和乳腺。使用唾液腺器官培养系统， 已经确定了一些分支所需的分子，包括 整合素、细胞外基质(ECM)和肌动蛋白细胞骨架，但 机制仍不清楚。分枝的第一步是形成裂隙。 在上皮表面。III型胶原蛋白已经定位于裂隙， 这表明它可能在裂隙的形成中起作用。整合素是异二聚体 跨越质膜并介导细胞外基质相互作用的分子 与肌动蛋白细胞骨架结合，因此很可能参与协调 参与分枝形态发生的细胞运动和/或形状变化。这 提案将解决整合素和肌动蛋白细胞骨架在 颌下腺发育有三个具体目标：1)确定角色 裂隙形成中的III型胶原，2)定义肌动蛋白重排和 裂隙形成所需的调节剂，以及3)确定是否有 黏附复合体聚集在裂隙形成部位。了解 唾液分支中细胞-基质接触的组成和功能 形态发生将导致对复杂发育的进一步理解 过程，并提供可能促进Rational开发的见解 癌症和干燥S综合征的唾液腺再生途径 病人。

DESCRIPTION: (provided by applicant) Branching morphogenesis is a complex process that occurs during the development of the salivary gland, lung, kidney, prostate, and mammary gland. Using the salivary gland organ culture system, some molecules required for branching have been identified, including integrins, the extracellular matrix (ECM), and the actin cytoskeleton, but mechanisms remain unclear. The first step in branching is formation of clefts in the epithelial surface. Collagen III has been localized to clefts, indicating it may play a role in cleft formation. Integrins are heterodimeric molecules, which span the plasma membrane and mediate interaction of the ECM with the actin cytoskeleton and are, therefore, likely involved in coordinating cell movements and/or shape changes involved in branching morphogenesis. This proposal will address the role of integrins and actin cytoskeleton in submandibular gland development with three specific aims: 1) identify the role of collagen III in cleft formation, 2) define the actin rearrangements and regulators required for cleft formation, and 3) determine if there is an adhesion complex assembled at the sites of cleft formation. Understanding the composition and function of cell-matrix contacts in salivary branching morphogenesis will lead to further understanding of complex developmental processes and provide insights that may facilitate development of rational approaches for salivary gland regeneration in cancer and Sjogren?s syndrome patients.