Collective mesendoderm migration relies on an intrinsic directionality signal transmitted through cell contacts
Dumortier, J.G., Martin, S., Meyer, D., Rosa, F.M., and David, N.B.
ABSTRACT
Collective cell migration is key to morphogenesis, wound healing, or cancer cell migration. However, its cellular bases are
just starting to be unraveled. During vertebrate gastrulation, axial mesendoderm migrates in a group, the prechordal plate,
from the embryonic organizer to the animal pole. How this collective migration is achieved remains unclear. Previous work
has suggested that cells migrate as individuals, with collective movement resulting from the addition of similar individual
cell behavior. Through extensive analyses of cell trajectories, morphologies, and polarization in zebrafish embryos, we reveal
that all prechordal plate cells show the same behavior and rely on the same signaling pathway to migrate, as expected if they
do so individually. However, by using cell transplants, we demonstrate that prechordal plate migration is a true collective
process, as isolated cells do not migrate toward the animal pole. They are still polarized 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 signaling, 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 neighbors. This self-organizing model could account
for collective invasion of new territories, as observed in cancer strands, without requirement for any attractant in the colonized
tissue.
