NEUROTROPHINS AND CARDIOGENESIS

描述（改编自申请人的摘要）： 该项目旨在确定神经营养因子-3（NT-3）：trk C信号转导的作用 在心脏形态发生过程中。 研究人员计划：（1）定义 NT-3和每种trk C受体亚型在心脏 发展，使用免疫组织化学和原位分析。 这些研究 将确定从转录本中选择性剪接trk C的时间 编码激酶活性蛋白的转录物， 酪氨酸激酶活性;（2）比较导致的心脏异常 从使用无效突变小鼠缺乏NT-3和trk C表达，到 定义这种神经营养因子的作用：受体系统在心脏神经 （3）直接检测trk的能力 C受体在体内调节心脏发生，使用复制缺陷 逆转录病毒介导trk C转基因在心肌细胞中的表达 鸡胚心肌细胞或心脏神经嵴。 逆转录病毒编码 全长或截短的trkC同种型将用于感染和标记 心肌细胞或神经嵴前体，以及转基因的能力， 改变这些细胞的迁移、增殖和分化能力， 细胞将被确定。

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.