A sphingosine-1-phosphate receptor regulates cell migration during vertebrate heart development
A sphingosine-1-phosphate receptor regulates cell migration during vertebrate heart development
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DOI：
10.1038/35018092
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发表时间：
2000-07-13
期刊：
影响因子：
64.8
通讯作者：
Stainier, DYR
中科院分区：
文献类型：
--
作者：
Kupperman, E;An, SZ;Stainier, DYR
协调的细胞迁移在许多基本的生物学过程中是必不可少的，包括胚胎发育、器官发生、伤口愈合和免疫应答。在器官发生过程中，细胞群被引导到胚胎内的特定位置。在这里，我们表明，斑马鱼英里间隔（mil）突变（1，2），特别是影响迁移的心脏前体的中线。我们发现，移植到野生型胚胎中的突变细胞迁移正常，而突变胚胎中的野生型细胞不能迁移，这表明mil可能参与产生允许迁移的环境。我们分离的位置克隆，并表明它编码的溶血鞘脂G蛋白偶联受体家族的成员。我们还表明，鞘氨醇-1-磷酸是Mil的配体，它激活几个下游信号转导事件，而不是激活的突变等位基因。这些数据揭示了lysosphingolipids在脊椎动物发育过程中调节细胞迁移的新作用，并为心脏器官发生过程中双侧心脏原基的融合提供了第一个分子线索。
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(1,2) 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.