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

Nature volume 406, pages 192–195 (2000)Cite this article

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) mutation1,2 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.

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Figure 1: mil phenotype.
Figure 2: S1P-induced intracellular Ca2+ mobilization (a) and MAP kinase activation (b) requires functional Mil receptors.
Figure 3: mil rescue and expression.

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Acknowledgements

We thank I. Herskowitz, H. Bourne, C. Bargmann, R. Lehmann and members of the lab for discussions and comments on the manuscript. We are also grateful to A. Navarro for excellent fish care. E.K. is supported by the University of California President's postdoctoral fellowship program. This work was supported in part by the Program in Human Genetics Genomics Core Facility at UCSF as well as by grants to D.Y.R.S. from the American Heart Association and the Packard Foundation.

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Authors and Affiliations

  1. Departments of Biochemistry and Biophysics and,

    Erik Kupperman, Nick Osborne, Steven Waldron & Didier Y. R. Stainier

  2. Medicine, Programs in Developmental Biology, Genetics and Human Genetics, University of California San Francisco, San Francisco, 94143-0448, California, USA

    Songzhu An

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Correspondence to Didier Y. R. Stainier.

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Kupperman, E., An, S., Osborne, N. et al. A sphingosine-1-phosphate receptor regulates cell migration during vertebrate heart development. Nature 406, 192–195 (2000). https://doi.org/10.1038/35018092

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