The mevalonate pathway controls heart formation in Drosophila by isoprenylation of Ggamma1.
The early morphogenetic mechanisms involved in heart formation are evolutionarily conserved. A screen for genes that control Drosophila heart development revealed a cardiac defect in which pericardial and cardial cells dissociate, which causes loss of cardiac function and embryonic lethality. This phenotype resulted from mutations in the genes encoding HMG-CoA reductase, downstream enzymes in the mevalonate pathway, and G protein Ggamma1, which is geranylgeranylated, thus representing an end point of isoprenoid biosynthesis. Our findings reveal a cardial cell-autonomous requirement of Ggamma1 geranylgeranylation for heart formation and suggest the involvement of the mevalonate pathway in congenital heart disease.[1]References
- The mevalonate pathway controls heart formation in Drosophila by isoprenylation of Ggamma1. Yi, P., Han, Z., Li, X., Olson, E.N. Science (2006) [Pubmed]
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