Kuriyama et al. describe how the phospholipid lysophosphatidic acid (LPA) stimulates N-cadherin endocytosis, allowing groups of neural crest cells to collectively migrate through Xenopus embryos.
During development and tumor metastasis, cells prepare to migrate by undergoing an epithelial-to-mesenchymal transition that loosens their connections to neighboring cells. Subsequently, however, many cell types, including neural crest cells, migrate en masse to their final destinations, indicating that their intercellular adhesions aren’t disrupted completely. Indeed, totally abolishing cell–cell contacts inhibits neural crest migration. Kuriyama et al. investigated the role of LPA and its receptor, LPAR2, in regulating neural crest motility.
Neural crest cells lacking LPAR2 failed to migrate out of the neural plate in Xenopus embryos. But LPAR2 knockdown had no effect on neural crest cell chemotaxis in vitro, unless the cells had to migrate through a narrow tunnel to reach the chemoattractant, re-creating the physical constraints the cells experience in vivo. Under these conditions, groups of LPAR2-deficient cells failed to enter the tunnels, whereas wild-type cells rearranged their intercellular contacts so that they could flow through the tunnel like water in a pipe.
Kuriyama et al. found that endocytosis of the adhesion receptor N-cadherin was inhibited in LPAR2-deficient neural crest cells, raising the protein’s surface levels and increasing intercellular adhesion. Partially inhibiting N-cadherin, or enhancing the protein’s endocytosis, restored the fluid-like behavior of LPAR2-depleted cells and rescued their ability to migrate through in vitro tunnels and embryonic tissues. Senior author Roberto Mayor now wants to investigate whether groups of metastasizing tumor cells show similar fluidity as they invade surrounding tissues.
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Text by Ben Short
