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Collective Mesendoderm Migration Relies on an Intrinsic Directionality Signal Transmitted through Cell Contacts

Dumortier, J, Martin, S., Meyer, D., Rosa, F. and David, N.B.

Collective cell migration is key to morphogenesis, wound healing, or cancer cell migration. However, its cellular bases are just starting to be unravelled. During Vertebrate gastrulation, axial mesendoderm migrates in group, the prechordal plate, from the embryonic organiser to the animal pole. How this collective migration is achieved remains unclear. Previous work has suggested that cells migrate as individuals, collective movement resulting from the addition of similar individual cell behaviour. Through extensive analyses of cell trajectories, morphologies and polarisation in zebrafish embryos, we reveal that all prechordal plate cells show the same behaviour and rely on the same signalling pathway to migrate, as expected if they do so individually. However, using cell transplants, we demonstrate that prechordal plate migration is a true collective process, since isolated cells do not migrate towards the animal pole. They are still polarised and motile but lose directionality. Directionality is restored upon contact with the endogenous prechordal plate. This contact dependent orientation relies on E-cadherin, Wnt-PCP signalling and Rac1. Importantly, groups of cells also need contact with the endogenous plate to orient correctly, showing an instructive role of the plate in establishing directionality. Overall, our results lead to an original model of collective migration in which directional information is contained within the moving group rather than provided by extrinsic cues, and constantly maintained in cells by contacts with their neighbours. This self-organising model could account for collective invasion of new territories, as observed in cancer strands, without requirement for any attractant in the colonised tissue.

PNAS 2012 ; published ahead of print October 1, 2012, doi:10.1073/pnas.1205870109