GROWTH FACTOR REGULATION OF CELL DIFFERENTIATION

细胞分化的生长因子调节

• 批准号: 3223306
• 负责人: ROBERT M GREENE
• 金额: $ 13万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-01 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3223306
• 关键词: cell differentiation; cell growth regulation; cleft palate; congenital oral /facial /cranial defect; embryogenesis; extracellular matrix; genetic transcription; growth /development; growth factor; growth factor receptors; growth inhibitors; laboratory mouse; mammalian embryology; mesenchyme; messenger RNA; mucopolysaccharides; neoplastic growth; palate; retinoate; teratogens; transforming growth factors

Successful investigations into the pathogenesis of cleft palate are hampered by an incomplete understanding of normal craniofacial ontogenesis in general and secondary palate formation in particular. Investigations dealing with characterization and regulation of basic developmental processes involved in normal craniofacial morphogenesis and dysmorphogenesis, therefore, are essential in that they contribute significantly toward the biological foundation necessary to design experiments aimed at clarifying the etiology of facial clefts. Although TGF-beta was initially described based on its ability to reversibly induce phenotypic transformation of fibroblastic cells, what has since emerged, is a concept of TGF-beta as a multifunctional regulatory peptide, involved in many developmental processes and controlling both growth and differentiation in an ever increasing diversity of cell and tissue types. In order to begin to examine the possible role that TGF-beta may play in palatal development, we are proposing to determine the relative amounts and localization of both TGF-beta and its mRNA in this embryonic tissue, investigate factors which may be responsible for positively and negatively regulating its action and characterize TGF-beta receptors_during palatal ontogeny. Cellular proliferation and synthesis of extracellular glycosaminoglycans and collagen has been shown to play a critical role in the normal ontogeny of the mammalian palate. The ability of TGF-beta to modulate extracellular matrix (ECM) accumulation is well documented and we propose to investigate the functional nature of these multifunctional molecules by determining 1) whether growth and/or synthesis of ECM components by cells derived from the developing embryonic palate are TGF-beta-mediated processes utilizing antisense oliaonucleotides to block expression of genes encoding for TGF-betas and 2). whether TGF-beta is capable of regulating ECM accumulation in embryonic palatal tissue either at the level of synthesis and/or degradation. The specific aims of this application include: 1- Determination of relative amounts and localization of TGF-beta in embryonic palatal tissue in vivo and in vitro, 2 - Determination of relative steady state levels, rates of transcription and localization of mRNA's for TGF-beta1, TGF-beta2 and TGF-beta3, 3 - Determination of whether growth and/or synthesis of ECM by embryonic palatal cells are TGF-beta-mediated processes, 4 - Characterization of TGF-beta receptors in developing palatal tissue and 5 - Analysis of biological responsiveness of embryonic palatal tissue to TGF-beta.

成功地研究了唇腭裂的发病机制 腭是阻碍了一个不完整的理解正常的 颅面个体发育和次生腭形成 特别是。 关于定性和 正常发育过程的基本调节 因此，颅面形态发生和畸形发生是 重要的是，它们对实现 设计实验所必需的生物学基础， 阐明了面部裂的病因 尽管TGF-β最初是基于其 可逆诱导表型转化的能力 成纤维细胞，后来出现的一个概念， TGF-β作为一种多功能调节肽，参与了许多 发展过程和控制双方的增长和 在不断增加的细胞和组织的多样性中分化 类型 为了开始研究 TGF-β可能在腭发育中起作用，我们建议 确定TGF-β的相对量和定位， 和它的mRNA在这个胚胎组织中，研究因素， 可能负责积极和消极地调节其 作用和表征TGF-β受体_在腭发育过程中。 细胞增殖和细胞外基质的合成 糖胺聚糖和胶原蛋白已经被证明在 在哺乳动物腭的正常个体发育中的作用。 的能力 TGF-β调节细胞外基质（ECM）的积累， 有据可查，我们建议调查功能 这些多功能分子的性质，通过确定1）是否 来源于细胞的细胞的ECM组分的生长和/或合成 发育胚胎腭是TGF-β介导的过程 利用反义寡核苷酸阻断基因表达 编码TGF-β和2）。TGF-β是否能够 调节胚胎腭组织中ECM的积累， 合成和/或降解的水平。 本申请的具体目的包括：1- TGF-β相对量和定位的测定 胚胎腭组织在体内和体外，2 -测定 相对稳定状态水平，转录速率和 TGF-β 1、TGF-β 2和TGF-β 3、3的mRNA定位 - 确定ECM的生长和/或合成是否通过 胚胎腭细胞是TGF-β介导的过程，4 - 发育中腭部组织TGF-β受体的特征 5 -胚胎腭突的生物学反应性分析 转化为TGF-β