PUBLICATION
Germ Cell Migration in Zebrafish Is Dependent on HMGCoA Reductase Activity and Prenylation
- Authors
- Thorpe, J.L., Doitsidou, M., Ho, S.-Y., Raz, E., and Farber, S.A.
- ID
- ZDB-PUB-040211-1
- Date
- 2004
- Source
- Developmental Cell 6: 5-302 (Journal)
- Registered Authors
- Doitsidou, Maria, Farber, Steven, Ho, Shiu-Ying, Raz, Erez, Thorpe, Juanita
- Keywords
- none
- MeSH Terms
-
- Animals
- Anticholesteremic Agents/pharmacology
- Atorvastatin
- Cell Movement/drug effects
- Cell Movement/genetics
- Cell Movement/physiology*
- Chemokine CXCL12
- Chemokines, CXC/metabolism
- Diterpenes/pharmacology
- Dose-Response Relationship, Drug
- Drug Interactions
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Enzyme Inhibitors/pharmacology
- Farnesol/pharmacology
- Germ Cells/drug effects
- Germ Cells/enzymology
- Germ Cells/physiology*
- Heptanoic Acids/pharmacology
- Hydroxymethylglutaryl CoA Reductases/genetics
- Hydroxymethylglutaryl CoA Reductases/physiology*
- Mevalonic Acid/pharmacology
- Microinjections/methods
- Morpholines/pharmacology
- Protein Prenylation/physiology*
- Pyrroles/pharmacology
- RNA, Messenger/metabolism
- RNA-Binding Proteins
- Somites/drug effects
- Time Factors
- Zebrafish
- Zebrafish Proteins/metabolism
- gamma-Glutamyltransferase/metabolism
- PubMed
- 14960282 Full text @ Dev. Cell
Citation
Thorpe, J.L., Doitsidou, M., Ho, S.-Y., Raz, E., and Farber, S.A. (2004) Germ Cell Migration in Zebrafish Is Dependent on HMGCoA Reductase Activity and Prenylation. Developmental Cell. 6:5-302.
Abstract
Hydroxymethylglutaryl coenzyme A reductase (HMGCoAR) is required for isoprenoid and cholesterol biosynthesis. In Drosophila, reduced HMGCoAR activity results in germ cell migration defects. We show that pharmacological HMGCoAR inhibition alters zebrafish development and germ cell migration. Embryos treated with atorvastatin (Lipitor) exhibited germ cell migration defects and mild morphologic abnormalities. The effects induced by atorvastatin were completely rescued by prior injection of mevalonate, the product of HMGCoAR activity, or the prenylation precursors farnesol and geranylgeraniol. In contrast, squalene, a cholesterol intermediate further down the pathway, failed to rescue statin-induced defects. Moreover, pharmacologic inhibition of geranylgeranyl transferase 1 (GGT1) protein prenylation activity also resulted in abnormal germ cell migration. Thus, our pharmacological inhibition-and-rescue approach provided detailed information about the elements of isoprenoid biosynthesis that contribute to germ cell migration. Together with data from Drosophila (Santos and Lehmann, 2004, this issue), our results highlight a conserved role for protein geranylgeranylation in this context.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping