MEDIATORS OF TGF BETA SIGNALING IN PALATE DEVELOPMENT

味觉发育中 TGF Beta 信号传导的调节因子

• 批准号: 2861944
• 负责人: JUDITH C KUSEK
• 金额: $ 4.53万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2861944
• 关键词: biological signal transduction; bone development; cell cycle; cell differentiation; cell growth regulation; developmental genetics; embryo /fetus tissue /cell culture; gel mobility shift assay; genetic transcription; immunoprecipitation; laboratory mouse; organ culture; palate; polymerase chain reaction; posttranslational modifications; protein binding; protein localization; protein structure function; retinoblastoma protein; transcription factor; transforming growth factors; vertebrate embryology; western blottings

To elucidate the signal transduction pathway (molecular and nuclear mechanisms of gene regulation) responsible for the effects of TGFbeta on proliferation and differentiation during palatal development. The embryonic development of the orofacial area requires precise patterns of proliferation and differentiation. Central to these processes is the cell cycle which functions to integrate the vast array of incoming information and to coordinate the complex cytoplasmic and nuclear processes leading to either division or differentiation. One of the pivotal regulators of the cell cycle is the E2F family of transcription factors which functions to control the expression of those genes necessary for passage through the restriction point and the subsequent replication of genetic material during the S phase. The activity of E2F is controlled by a number of factors including formation of complexes with the products of the Retinoblastoma gene family (pRb, p107, p130). Although much is known concerning the role of E2Fs and pRbs in disturbances of growth and differentiation such as malignancy, their role in palatal development and the effects of various growth factors on their function has yet to be delineated. One growth factor having profound effects on the developing palate is TGFbeta which inhibits cellular proliferation and stimulates synthesis of extracellular matrix in palatal mesenchymal cells while also inducing differentiation of the medial edge epithelium. Since TGFbeta is known to affect multiple components of the cell cycle (including the pRbs and E2Fs) in other tissues and cell types, our hypothesis is that TGFbeta influences craniofacial development via an arrest of the cell cycle which is mediated by changes in the expression and the activity of the E2F family of transcription factors and by alterations in the interactions between the E2Fs and the Rb family of phosphoproteins.

阐明转化生长因子β（TGF β）对腭发育过程中细胞增殖和分化的影响的信号转导途径（基因调控的分子和核机制）。口面区域的胚胎发育需要精确的增殖和分化模式。 这些过程的中心是细胞周期，其功能是整合大量传入信息，并协调复杂的细胞质和核过程，导致分裂或分化。 细胞周期的关键调节因子之一是转录因子的E2F家族，其功能是控制通过限制点所必需的那些基因的表达和随后在S期期间遗传物质的复制。 E2F的活性受许多因素控制，包括与视网膜母细胞瘤基因家族（pRb，p107，p130）产物形成复合物。 虽然很多人都知道E2Fs和PRBs在生长和分化障碍，如恶性肿瘤的作用，他们在腭发育的作用和各种生长因子对他们的功能的影响还有待划定。对发育中的腭具有深远影响的一种生长因子是TGF β，其抑制细胞增殖并刺激腭间充质细胞中细胞外基质的合成，同时还诱导内侧边缘上皮的分化。 由于已知TGF β影响其他组织和细胞类型中细胞周期的多个组分（包括pRb和E2F），我们的假设是TGF β通过细胞周期的停滞影响颅面发育，细胞周期的停滞由E2F家族转录因子的表达和活性的变化以及E2F和Rb家族磷蛋白之间的相互作用的改变介导。