Kupperman et al. characterized the miles apart (mil) gene in zebrafish, which encodes a G protein-coupled receptor with sequence similarity to sphinosine-1-phosphate (S1P) receptors. Mutations in mil cause defects in the migration of cardiac precursor cells without affecting differentiation and lead to the formation of two laterally positioned hearts. Using transgenic methods, the authors show that mil expression was not required in the precursor cells themselves but was critical for establishing a signal or environment allowing proper migration. Confirmation that Mil is an S1P receptor came from the ability of S1P to stimulate calcium transients and to activate MAP kinase cascades in cells transfected to express mil. The data provide evidence for a role for lysosphingolipids in embryogenesis and signaling cell migration.
Kupperman, E., An, S., Osborne, N., Waldron, S., and Stainler, D.Y.R. (2000) A sphingosine-1-phosphate receptor regulates cell migration during vertebrate heart development. Nature 406: 192-195. [Online Journal]