EMBRYONIC SALIVARY GLAND MORPHOGENESIS

胚胎唾液腺形态发生

• 批准号: 2749359
• 负责人: TINA JASKOLL
• 金额: $ 23.67万
• 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/2749359
• 关键词: acinar cell; biological signal transduction; cell cycle; cell differentiation; cyclin dependent kinase; 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）：主要目标