Editors' ChoiceCell Migration

Complement, Attraction, and Collective Migration

Science Signaling  20 Dec 2011:
Vol. 4, Issue 204, pp. ec352
DOI: 10.1126/scisignal.4204ec352

Collective migration, in which cells move in a coordinated manner as a group, is important during development and in the movement of mesenchymal cells during metastasis. Within the migrating population, cell-cell adhesive forces are weaker than those of epithelial cells, which suggests that other mechanisms are responsible for the mutual attraction of cells within the group. Carmona-Fontaine et al. studied the collective migration of Xenopus and zebrafish neural crest (NC) cells, an embryonic cell population that undergoes an epithelial-to-mesenchymal transition (EMT) before exhibiting collective migration. Mathematical modeling and analysis of the migration of NC cell explants across a matrix in vitro suggested that an active mutual attraction mechanism was required to counterbalance the repulsive forces exerted by the matrix. A screen of proteins secreted by NC cells identified the complement component C3a. In vitro chemotaxis assays showed that C3a stimulated the chemotaxis of NC cells, which was prevented by blocking the C3a receptor (C3aR), which was present on migratory, but not premigratory, NC cells. Interfering with C3a or C3aR function prevented an NC graft from joining with endogenous NC cells in embryos and also enhanced the dispersion of NC cell clusters. Blocking C3aR function also impaired the collective migration of NC cells to the chemokine Sdf1 in vitro. C3a-C3aR interactions had no effect on cell-cell adhesion or on adhesion of the cells to fibronectin. Live imaging of NC cell migration in embryos showed that NC cells deficient in C3aR or treated with blocking antibody against C3a lost their ability to collectively migrate and became dispersed. Together, these data suggest that C3a and its receptor underlie the mutual attraction of NC cells, enabling the cells to migrate as a group in a coordinated manner.

C. Carmona-Fontaine, E. Theveneau, A. Tzekou, M. Tada, M. Woods, K. M. Page, M. Parsons, J. D. Lambris, R. Mayor, Complement fragment C3a controls mutual cell attraction during collective cell migration. Dev. Cell 21, 1026–1037 (2011). [PubMed]