NEUROTROPHINS AND CARDIOGENESIS

描述(改编自申请人的摘要)：本报告的目的 项目是确定神经营养素-3(NT-3)的作用：Trk C信号 在心脏形态发生过程中。调查人员计划：(1)界定 心脏发育过程中NT-3及各受体亚型的表达 应用免疫组织化学和原位分析技术进行研究。这些研究 将确定从转录本中选择性剪接trk C的时间 编码激酶活性蛋白，到编码缺乏蛋白的转录本 酪氨酸激酶活性；(2)比较导致的心脏异常 从零突变小鼠缺乏NT-3和trk C的表达，到 明确这种神经营养因子：受体系统在心脏神经中的作用 Crest与心肌细胞发育；(3)直接检测trk能力。 利用复制缺陷在体内调节心脏生成的C受体 逆转录病毒介导trk C转基因在心脏中的表达 鸡胚的心肌细胞或心脏神经脊。逆转录病毒编码 全长或截短的trk C亚型将用于感染和标记 心肌细胞或神经脊前体细胞与转基因能力 为了改变这些细胞的迁移、增殖和分化能力 牢房将被确定。

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.