NEUROTROPHINS AND CARDIOGENESIS

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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.