Editors' ChoiceCell Migration

Contact repels neural crest cells

See allHide authors and affiliations

Science Signaling  01 Sep 2015:
Vol. 8, Issue 392, pp. ec246
DOI: 10.1126/scisignal.aad3230

Whereas migrating epithelial cells establish and maintain cell-cell contacts when they touch one another, migrating fibroblasts establish only transient cell-cell contacts before repolarizing and moving away from one another, a phenomenon called contact inhibition of locomotion (CIL; see Priya and Yap). CIL is required for proper migration of neural crest (NC) cells in vertebrate embryos, and loss of CIL has been implicated in tumor cell invasiveness. NC cells undergo an epithelial-to-mesenchymal transition (EMT) and migrate from the neural plate to the periphery. Scarpa et al. found that most premigratory NC cells isolated from Xenopus laevis embryos behaved like epithelial cells, establishing stable cell junctions when they came into contact with each other. In contrast, most migratory NC cells formed cell junctions only transiently after contacting one another and formed lamellipodia that were oriented away from sites of cell-cell contact. During EMT, cells switch from producing the cell adhesion protein E-cadherin to producing N-cadherin. Overexpression of E-cadherin, but not N-cadherin, in NC cells reduced their migration in vivo and prevented CIL in vitro. Premigratory NC cells explanted from embryos injected with a morpholinoligonucleotide that targets E-cadherin showed increased CIL. In premigratory NC cells and in migratory NC cells overexpressing E-cadherin, Rac1 activity was high at sites of cell-cell contact and low at the free edges. Conversely, Rac1 activity was low at cell-cell contacts and high at the free edges in migratory NC cells. Redistribution of Rac1 activity in migratory NC cells depended on p120-catenin, which is a cadherin-associated component of cell junctions that stimulates Rac1 activity. Experiments using photoactivatable wild-type and dominant-negative forms of Rac1 demonstrated that redistribution of Rac1 activity to the free edges induced repolarization and separation of NC cells. Traction force microscopy revealed that traction forces in premigratory NCs were randomly distributed, whereas traction forces in migratory NCs were directed away from cell-cell contacts. Thus, prior to EMT, E-cadherin mediates the formation of stable junctions, and Rac1 activity is concentrated at sites of cell-cell contact, keeping NC cells together. After the loss of E-cadherin during EMT, cell contact causes Rac1 activity to relocalize to free edges away from cell-cell contacts, which initiates the formation of lamellipodia that generate traction forces to drive cell separation.

E. Scarpa, A. Szabó, A. Bibonne, E. Theveneau, M. Parsons, R. Mayor, Cadherin switch during EMT in neural crest cells leads to contact inhibition of locomotion via repolarization of forces. Dev. Cell 34, 421–434 (2015). [PubMed]

R. Priya, A. S. Yap, Making a choice: How cadherin switching controls cell migration. Dev. Cell 34, 383–384 (2015). [PubMed]

Stay Connected to Science Signaling