REGULATION OF BRANCHING MORPHOGENESIS OF SALIVARY GLAND

描述（改编自申请人的摘要）：上皮细胞 间充质（E-M）相互作用在发育中起主要作用， 上皮器官 大多数关于这些E-M的机制的分析 相互作用集中在细胞外基质的成分上， （ECM）。 细胞粘附分子的研究进展 现在提供了一个机会来检查实际上皮细胞的作用， 细胞在这些相互作用。 整合素构成一类细胞 作为特定ECM成分受体的表面蛋白。 胎鼠的下颌下腺（SMG）呈现良好的 特征系统研究上皮间充质相互作用， 在体内和体外。 已发表的研究和主要研究者的初步数据 表明EGF和TGF α促进SMG发育， 培养，而EGF受体的抑制剂（tyrphostin）减少 SMG的成长和发展。 研究人员推测，这些 生长因子可能通过调节SMG的发育， 整合素在上皮细胞上的表达，这随后决定了 它们在发育过程中与间充质相互作用的性质。 为解决这一假设，提出了三个具体目标： 1)表征整合素和ECM组分的表达 在SMG体内和体外开发过程中， 这些分子的扰动干扰SMG的正常发育。 2)描述EGF和TGF α对SMG发育的影响 并确定这些生长因子是否调节 整合素及其ECM配体。 3)为了确定EGF和TGF α是否是 SMG的发展，并确定他们是否产生的间充质 SMG的细胞。 这些研究的结果有望增进对SMG的理解 发展动态，并可能产生洞察对方 SMG上皮间质相互作用影响的过程， 伤口愈合、转移和先天性 畸形

DESCRIPTION (Adapted from the Applicant's Abstract): Epithelial- mesenchymal (E-M) interactions play primary roles in development of epithelial organs. Most analyses of mechanisms mediating these E-M interactions have focused on components of the extracellular matrix (ECM). Recent advances in our understanding of cell adhesion molecules now afford an opportunity to examine the role of the actual epithelial cells in these interactions. Integrins constitute a class of cell surface proteins that serve as receptors for specific ECM components. The submandibular gland (SMG) of the fetal mouse presents a well characterized system to study epithelial-mesenchymal interactions both in vivo and in vitro. Published studies and preliminary data of the PI indicate that EGF and TGF alpha promote development of the SMG in culture, while an inhibitor of the EGF receptor (tyrphostin) diminishes SMG growth and development. The investigators hypothesize that these growth factors may be influencing SMG development by regulating expression of integrins on epithelial cells, which subsequently dictates the nature of their interactions with the mesenchyme during development. Three Specific Aims are proposed to address this hypothesis: 1) To characterize the expression of integrins and ECM components during development of the SMG in vivo and in vitro and to establish if perturbations of these molecules interferes with normal SMG development. 2) To characterize the effects of EGF and TGF alpha on SMG development in vitro and to determine if these growth factors regulate expression of integrins and their ECM ligands. 3) To establish whether EGF and TGF alpha are physiologic regulators of SMG development and to determine whether they are produced by mesenchymal cells of the SMG. Results of these studies are expected to enhance the understanding of SMG developmental dynamics and potentially yield insight into the other processes impacted on by SMG epithelial mesenchymal interactions such as wound healing, metastasis and the genesis of congenital malformations.