Sci. STKE, 5 September 2006
DEVELOPMENT Holding the Heart Together
To elucidate molecular mechanisms in heart development, Yi et al. have used a genetic screen for Drosophila mutants. Five mutants were observed in which the cardioblast layer of the heart does not adhere to the adjacent layer of pericardial cells. This phenotype is labeled as "broken hearted." Gene cloning shows that this phenotype arises from mutations in genes that encode components of the geranylgeranyl synthesis pathway downstream of HMG-CoA reductase. Statins inhibit this pathway, and treatment with statins during development yielded a similar phenotype. Hence, isoprenoid biosynthesis functions in heart development, with defects in geranylgeranylation of the G-protein G1 causing severe defects in heart formation because of abnormal adhesion of cardioblasts to pericardial cells. Because of the conservation of mechanisms in heart formation, these findings may illuminate mammalian heart development and congenital heart disease and also the effects of statins on heart function.
Citation: Holding the Heart Together. Sci. STKE 2006, tw307 (2006).
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