ROLE OF FGF RECEPTOR SIGNALING IN CARDIAC DEVELOPMENT

University Of California San Diego, La Jolla CA

Investigators

Abstract

Cardiogenesis, the induction and subsequent development of the heart, is one of the most critical events in embryonic development. Indeed, defects in cardiac development are responsible for a large proportion of embryonic lethality in humans. Signaling by fibroblast growth factor receptors (FGFRs) has been implicated in diverse developmental processes, including induction of mesoderm (the source of cardiogenic tissue) and embryonic cardiomyocyte proliferation. However, specific requirements for FGFR signaling in vertebrate heart development are unknown. The hypothesis of this proposal is that FGFR signaling is required for heart development in a temporally- specific manner throughout vertebrate cardiogenesis. Xenopus laevis, the South African Clawed frog, is an ideal model organism for addressing this hypothesis in vivo. The specific aims are to; (1) ectopically express a dominant-negative mutant of the Xenopus FGFR (dnFGFR) at early (pregastrula) stages in Xenopus embryos, and determine its effect(s) on heart development; (2) investigate whether cardiogenesis is mediated downstream of FGFR signaling by the Ets-type transcription factor XER81. This will be done through expression of a dominant-negative mutant of XER81 at early stages in Xenopus and determining its effect(s) on cardiogenesis; (3) examine specific requirements for FGFR signaling throughout cardiogenesis by temporally-controlling expression of dnFGFR and dnXER81.