NEUROTROPHINS AND CARDIOGENESIS

神经营养素和心脏发生

• 批准号: 6343587
• 负责人: BARBARA L HEMPSTEAD
• 金额: $ 28.24万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-28 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6343587
• 关键词: RNA splicing; animal genetic material tag; chick embryo; developmental genetics; developmental neurobiology; embryogenesis; enzyme activity; enzyme induction /repression; gene mutation; genetically modified animals; growth factor receptors; heart; human fetus tissue; isozymes; laboratory mouse; mammalian embryology; myocardium; myogenesis; neural crest; neurogenesis; neurotrophic factors; protein tyrosine kinase; tissue /cell culture

DESCRIPTION (adapted from the applicant's abstract): The aim of this project is to define the role of neurotrophin-3 (NT-3):trk C signaling during cardiac morphogenesis. The investigators plan to: (1) define the expression of NT-3, and each trk C receptor isoform during cardiac development, using immunohistochemistry and in situ analysis. These studies will define the timing of alternative splicing of trk C from transcripts encoding kinase active proteins, to transcripts encoding proteins lacking tyrosine kinase activity; (2) compare the cardiac abnormalities resulting from the lack of expression of NT-3 and trk C using null mutant mice, to define the roles of this neurotrophin:receptor system in cardiac neural crest and cardiac myocyte development; (3) directly test the ability of trk C receptors to modulate cardiogenesis in vivo, using replication defective retroviruses to direct the expression of trk C transgenes in cardiac myocytes or cardiac neural crest of chicken embryos. Retroviruses encoding the full length or truncated trk C isoforms will be used to infect and tag cardiac myocyte or neural crest precursors, and the ability of the transgene to modify the migratory, proliferative and differentiative capacity of these cells will be determined.

描述（改编自申请人的摘要）：目的 项目是定义Neurotrophin-3（NT-3）的作用：TRK C信号传导 在心脏形态发生期间。 调查人员计划：（1）定义 心脏中NT-3和每个TRK C受体同工型的表达 开发，使用免疫组织化学和原位分析。 这些研究 将定义转录本的替代剪接的时间安排 编码激酶活性蛋白，编码编码缺乏蛋白质的成绩单 酪氨酸激酶活性； （2）比较导致的心脏异常 由于使用无效突变小鼠缺乏NT-3和TRK C的表达，到 定义这种神经营养蛋白的作用：受体系统在心脏神经中 波峰和心肌细胞发育； （3）直接测试TRK的能力 C受体在体内调节心脏发生，使用复制有缺陷 逆转录病毒指导TRK C转基因在心脏中的表达 鸡胚胎的心肌细胞或心脏神经波峰。 逆转录病毒编码 全长或截短的TRK C同工型将用于感染和标记 心肌细胞或神经rest前体以及转基因的能力 修改这些迁徙，增生和分化能力 将确定细胞。