PUBLICATION

A sphingosine-1-phosphate receptor regulates cell migration during vertebrate heart development

Authors
Kupperman, E., An, S., Osborne, N., Waldron, S., and Stainier, D.Y.
ID
ZDB-PUB-000824-19
Date
2000
Source
Nature   406(6792): 192-195 (Journal)
Registered Authors
Kupperman, Erik, Osborne, Nick, Stainier, Didier
Keywords
none
MeSH Terms
  • Alleles
  • Animals
  • Cell Movement
  • Cloning, Molecular
  • Embryonic and Fetal Development
  • GTP-Binding Proteins/metabolism
  • Heart/embryology*
  • Humans
  • Jurkat Cells
  • Lysophospholipids*
  • Molecular Sequence Data
  • Mutation
  • Myocardium/cytology
  • Myocardium/metabolism
  • Receptors, Cell Surface/physiology*
  • Receptors, G-Protein-Coupled*
  • Receptors, Lysophospholipid
  • Sphingosine/analogs & derivatives*
  • Sphingosine/metabolism
  • Transfection
  • Transplantation Chimera
  • Zebrafish
PubMed
10910360 Full text @ Nature
Abstract
Coordinated cell migration is essential in many fundamental biological processes including embryonic development, organogenesis, wound healing and the immune response. During organogenesis, groups of cells are directed to specific locations within the embryo. Here we show that the zebrafish miles apart (mil) mutation specifically affects the migration of the heart precursors to the midline. We found that mutant cells transplanted into a wild-type embryo migrate normally and that wild-type cells in a mutant embryo fail to migrate, suggesting that mil may be involved in generating an environment permissive for migration. We isolated mil by positional cloning and show that it encodes a member of the lysosphingolipid G-protein-coupled receptor family. We also show that sphingosine-1-phosphate is a ligand for Mil, and that it activates several downstream signalling events that are not activated by the mutant alleles. These data reveal a new role for lysosphingolipids in regulating cell migration during vertebrate development and provide the first molecular clues into the fusion of the bilateral heart primordia during organogenesis of the heart.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping