EMBRYONIC SALIVARY GLAND MORPHOGENESIS

胚胎唾液腺形态发生

• 批准号: 2458657
• 负责人: TINA JASKOLL
• 金额: $ 22.83万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-30 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2458657
• 关键词: acinar cell; biological signal transduction; cell cycle; cell differentiation; cyclins; embryonic stem cell; enzyme linked immunosorbent assay; epidermal growth factor; epithelium; glucocorticoids; growth factor receptors; histogenesis; hormone regulation /control mechanism; immunocytochemistry; in situ hybridization; laboratory mouse; messenger RNA; mucins; receptor expression; steroid hormone receptor; submandibular gland; tissue /cell culture; transforming growth factors; tumor necrosis factor alpha; western blottings

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.

描述（改编自申请人摘要）：主要目的 这项研究的目的是研究 糖皮质激素（CORT）在胚胎唾液腺发育过程中的作用。 已发表的和初步的研究表明，CORT及其受体（GR） 调节唾液腺分支和组织分化 特定的生长和发育因素。 该提案将使用一个在 体外模型系统，以测试假设（1）CORT-GR介导的 特异性生长因子/受体（TGF-β、TNF-α或EGF-R）的表达是 调节形态分化的关键分子机制， （2）CORT-GR的调节 Msx2在上皮-间充质相互作用位点的表达起着重要作用。 在胚胎唾液腺形态发生中的关键作用;（3）CORT-GR 介导的上皮细胞增殖的增强最有可能是通过一个 或更多的TGF-β。细胞周期蛋白-cdk和/或TGF-β。N-myc途径。 具体目标 目的是：（1）阐明CORT-GR介导的胚胎发育的分子机制 颌下腺形态调节的分子机制 CORT调节的Msx2介导的胚胎下颌下腺的细节 探讨TGF-β 2、TGF-β 3、p27、 cdk4、cyclin E和N-myc在上皮细胞CORT-GR调节中的作用 增殖和分枝形态发生。 生成的数据将 描述CORT-GR介导的形态调节的分子机制， 胚胎颌下腺发育与鉴定相关 后续体内研究的形态调节途径 问题研究 由于唾液腺在出生后继续发育， 研究最终可能会为新的激素，生长， 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以用于治疗成人 唾液腺疾病