EMBRYONIC SALIVARY GLAND MORPHOGENESIS

描述(改编自申请人的摘要)：主要目标 这项拟议的研究的目的是调查脑组织的形态调节 胚胎唾液腺发育过程中的糖皮质激素(CORT)。 已发表的和初步的研究表明，皮质醇及其受体(GR) 通过调节调节唾液腺分支和组织分化 特定的生长和发育因素。此提案将使用in 体外模型系统，以检验(1)CORT-GR介导的假设 特异性生长因子/受体(转化生长因子-b、肿瘤坏死因子-a或表皮生长因子受体)的表达是 调控形态分化和细胞分化的关键分子机制 胚胎唾液腺的组织分化；(2)皮质醇-GR调节 MSX2在上皮-间充质相互作用部位的表达 在胚胎唾液腺形态发生中的关键作用；以及(3)皮质醇受体 介导的促进上皮细胞增殖很可能是通过一种 或更多的转化生长因子-β.细胞周期蛋白-cdk和/或转化生长因子-β.N-myc途径(S)。具体目标 目的是：(1)阐明皮质醇受体介导的胚胎发育的分子机制 颌下腺形态调节；(2)分子生物学研究 皮质醇调节的MSX2介导的胚胎颌下腺的细节 (3)研究转化生长因子-β2、转化生长因子-β3、p27、 CDK4、Cyclin E和N-myc在上皮细胞皮质醇-GR调节中的作用 增殖和分枝形态发生。生成的数据将 皮质醇-GR介导的细胞形态调节的分子机制 胚胎性颌下腺发育及相关鉴定 后续在体研究的形态调节途径(S) 学习。由于唾液腺在出生后继续发育，这些 研究可能最终为新的激素、生长提供新的见解 先天性结构异常的因素或其他治疗策略 或功能。这样的治疗策略甚至可能在治疗成人 唾液腺疾病。

DESCRIPTION (Adapted from the applicant's Abstract): The primary objective of the proposed research is to investigate the morphoregulatory role of glucocorticoids (CORT) during embryonic salivary gland development. Published and preliminary studies indicate that CORT, with its receptor (GR) regulate salivary gland branching and histodifferentiation by regulating specific growth and developmental factors. This proposal will use an in vitro model system to test the hypotheses that (1) CORT-GR-mediated expression of specific growth factors/receptors (TGF-b, TNF-a, or EGF-R) is a key molecular mechanism regulating morphodifferentiation and histodifferentiation of the embryonic salivary gland; (2) CORT-GR modulation of Msx2 expression at sites of epithelial-mesenchymal interaction plays a critical role during embryonic salivary gland morphogenesis; and (3) CORT-GR mediated enhancement of epithelial cell proliferation is most likely via one or more TGF-b..cyclin-cdk and/or TGF-b..N-myc pathway(s). The specific aims are to: (1) elucidate the molecular mechanism of CORT-GR-mediated embryonic submandibular gland morphoregulation; (2) to investigate the molecular details of CORT-modulated Msx2-mediated embryonic submandibular gland morphogenesis, and (3) to investigate the roles of TGF-b2, TGF-b3, p27, cdk4, cyclin E and N-myc in CORT-GR modulation of epithelial cell proliferation and branching morphogenesis. The data generated will delineate molecular mechanisms of CORT-GR mediated morphoregulation of embryonic submandibular gland development and identify relevant morphoregulatory pathway(s) to be investigated in subsequent in vivo studies. Since salivary glands continue to develop after birth, these studies may eventually provide new insights into novel hormone, growth factor, or other treatment strategies for congenital anomalies of structure or function. Such treatment strategies may even be useful in treating adult salivary gland disease.