Ruth Lehmann is a developmental and cell biologist at the New York University School of Medicine, where she is the Director of the Skirball Institute of Biomolecular Medicine, the Laura and Isaac Perlmutter Professor of Cell Biology, and the Chair of the Department of Cell Bio...
Isoprenoids Control Germ Cell Migration Downstream of HMGCoA Reductase
- Citation data:
Developmental Cell, ISSN: 1534-5807, Vol: 6, Issue: 2, Page: 283-293
- Publication Year:
- Biochemistry, Genetics and Molecular Biology
3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAr) provides attractive cues to Drosophila germ cells, guiding them toward the embryonic gonad. However, it remains unclear how HMGCoAr mediates this attraction. In a genomic analysis of the HMGCoAr pathway, we found that the fly genome lacks several enzymes required for cholesterol biosynthesis, ruling out cholesterol and cholesterol-derived proteins as mediators of PGC migration. Genetic analysis of the pathway revealed that two enzymes, farnesyl-diphosphate synthase and geranylgeranyl-diphosphate synthase, required for the production of isoprenoids, act downstream of HMGCoAr in germ cell migration. Consistent with a role in geranylgeranylation, embryos deficient in geranylgeranyl transferase type I show germ cell migration defects. Our data, together with similar findings in zebrafish, implicate an isoprenylated protein in germ cell attraction. The specificity and evolutionary conservation of the HMGCoAr pathway for germ cells suggest that an attractant common to invertebrates and vertebrates guides germ cells in early embryos.