PUBLICATION
A Mutation in Zebrafish hmgcr1b Reveals a Role for Isoprenoids in Vertebrate Heart-Tube Formation
- Authors
- D'Amico, L., Scott, I.C., Jungblut, B., and Stainier, D.Y.
- ID
- ZDB-PUB-070212-31
- Date
- 2007
- Source
- Current biology : CB 17(3): 252-259 (Journal)
- Registered Authors
- D'Amico, Leonard, Jungblut, Benno, Scott, Ian, Stainier, Didier
- Keywords
- none
- MeSH Terms
-
- Animals, Genetically Modified
- Embryo, Nonmammalian/metabolism
- Phenotype
- Amino Acid Substitution
- Myocardium/cytology
- Animals
- Protein Prenylation*
- Epithelial Cells/cytology
- Morphogenesis*
- Zebrafish/embryology*
- Zebrafish/genetics
- Sequence Alignment
- Mevalonic Acid
- Cell Movement
- Myocytes, Cardiac/cytology
- Hydroxymethylglutaryl CoA Reductases/chemistry
- Hydroxymethylglutaryl CoA Reductases/genetics
- Hydroxymethylglutaryl CoA Reductases/metabolism*
- Zebrafish Proteins/metabolism*
- Amino Acid Sequence
- Heart/embryology*
- Point Mutation
- Gene Expression Regulation, Developmental*
- Molecular Sequence Data
- PubMed
- 17276918 Full text @ Curr. Biol.
Citation
D'Amico, L., Scott, I.C., Jungblut, B., and Stainier, D.Y. (2007) A Mutation in Zebrafish hmgcr1b Reveals a Role for Isoprenoids in Vertebrate Heart-Tube Formation. Current biology : CB. 17(3):252-259.
Abstract
In vertebrates, the morphogenetic assembly of the primitive heart tube requires the medial migration and midline fusion of the bilateral myocardial epithelia . Several mutations that result in abnormal heart-tube formation have been studied; however, an understanding of the underlying molecular and cellular mechanisms of the migration and fusion of these epithelial sheets is far from complete . In a forward genetic screen to identify genes regulating early zebrafish heart development, we identified a mutation in the 3-hydroxy-3-methylglutaryl-Coenzyme A reductase 1b (hmgcr1b) gene that affects myocardial migration to the midline and subsequent heart-tube morphogenesis. The mutant phenotype can be rescued with injections of mevalonate, the direct product of HMGCR activity. Furthermore, treatment of embryos with pharmacological inhibitors of isoprenoid synthesis, which occurs downstream of mevalonate production, resulted in defective heart-tube formation. Interestingly, in hmgcr1b mutant embryos and embryos treated with HMGCR inhibitors, both RasCT20-eGFP and RhoaCT32-eGFP fusion proteins were mislocalized away from the plasma membrane in embryonic myocardial cells. We conclude that protein prenylation, acting downstream of Hmgcr1b and possibly through Ras and, or, Rho signaling, is required for the morphogenesis of the myocardial sheets for formation of the primitive heart tube.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping