ECM, integrins, and action in salivary morphogenesis

描述：（由申请人提供）分支形态发生是一个复杂的 这一过程发生在唾液腺，肺，肾， 前列腺和乳腺。利用涎腺器官培养系统， 已经确定了一些支化所需的分子，包括 整合素，细胞外基质（ECM）和肌动蛋白细胞骨架，但 机制尚不清楚。分枝的第一步是形成裂缝 在上皮表面。胶原蛋白III已经定位于裂缝， 表明它可能在裂缝形成中起作用。整合素是异二聚体 分子，其跨越质膜并介导ECM的相互作用 与肌动蛋白细胞骨架，因此，可能参与协调 涉及分支形态发生的细胞运动和/或形状变化。这 该提案将讨论整合素和肌动蛋白细胞骨架在 下颌下腺发育有三个具体目标：1）确定作用 2）确定肌动蛋白重排， 裂缝形成所需的调节剂，以及3）确定是否存在 粘附复合物在裂缝形成的部位组装。了解 唾液分支中细胞-基质接触的组成和功能 形态发生将导致进一步了解复杂的发育 过程，并提供见解，可能有助于制定合理的 癌症和干燥综合征中唾液腺再生的方法氏综合征 患者

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.