Isoprenoids control germ cell migration downstream of HMGCoA reductase

Dev Cell. 2004 Feb;6(2):283-93. doi: 10.1016/s1534-5807(04)00023-1.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkyl and Aryl Transferases / genetics
  • Alkyl and Aryl Transferases / metabolism
  • Animals
  • Animals, Genetically Modified
  • Cell Movement / drug effects*
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Cloning, Molecular
  • Dimethylallyltranstransferase
  • Drosophila
  • Drosophila Proteins
  • Embryo, Nonmammalian / cytology*
  • Embryo, Nonmammalian / physiology
  • Farnesyl-Diphosphate Farnesyltransferase / genetics
  • Farnesyl-Diphosphate Farnesyltransferase / metabolism
  • Gene Expression Profiling / methods
  • Gene Expression Regulation
  • Geranylgeranyl-Diphosphate Geranylgeranyltransferase
  • Germ Cells / drug effects*
  • Germ Cells / physiology
  • Hydroxymethylglutaryl CoA Reductases / genetics
  • Hydroxymethylglutaryl CoA Reductases / physiology*
  • Immunohistochemistry / methods
  • In Situ Hybridization / methods
  • Mesoderm / metabolism
  • Mutation
  • Nervous System / embryology
  • Nervous System / metabolism
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism
  • RNA, Messenger / metabolism
  • Terpenes / chemistry
  • Terpenes / pharmacology*

Substances

  • Drosophila Proteins
  • RNA, Messenger
  • Terpenes
  • Oxidoreductases
  • Hydroxymethylglutaryl CoA Reductases
  • Alkyl and Aryl Transferases
  • Dimethylallyltranstransferase
  • QM protein, Drosophila
  • Farnesyl-Diphosphate Farnesyltransferase
  • Geranylgeranyl-Diphosphate Geranylgeranyltransferase