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Science 313 (5791): 1301-1303

Copyright © 2006 by the American Association for the Advancement of Science

The Mevalonate Pathway Controls Heart Formation in Drosophila by Isoprenylation of G{gamma}1

Peng Yi,* Zhe Han,*{dagger} Xiumin Li, Eric N. Olson{dagger}

Abstract: 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 G{gamma}1, which is geranylgeranylated, thus representing an end point of isoprenoid biosynthesis. Our findings reveal a cardial cell–autonomous requirement of G{gamma}1 geranylgeranylation for heart formation and suggest the involvement of the mevalonate pathway in congenital heart disease.

Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390–9148, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: zhe.han{at}utsouthwestern.edu (Z.H.); eric.olson{at}utsouthwestern.edu (E.N.O.)

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