Collective mesendoderm migration relies on an intrinsic directionality signal transmitted through cell contacts

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.embryogenesis | cell movement | 3D tracking

Dynamic intracellular distribution of Vangl2 during cell polarization in zebrafish gastrula

“…At the onset of gastrulation, internalized lateral mesodermal and endodermal cells initially move anteriorly, and at mid-gastrulation turn their trajectories towards the dorsal midline (Dumortier et al, 2012;. In order to better understand the relationship between the cell body alignment and this movement behavior, we analyzed the trajectories of WT and vangl2 mutant cells.…”

Collective cell migration in development

“…Transplant experiments show that isolated prechordal plate cells are unable to migrate directionally until they make contact with the rest of the collective (Dumortier et al, 2012). Importantly, this work suggested that intrinsic directional information might arise from cell-cell interactions independently of guidance cues (Dumortier et al, 2012). Does contact-dependent polarity also occur in migratory epithelial collectives?…”

“…Although the role of CIL in controlling directional migration of the neural crest is well established Theveneau et al, 2010Theveneau et al, , 2013, accumulating evidence suggests that CIL is present in other collective migration systems as well. Recent work has shown that Wnt/PCP-mediated contact-dependent polarity drives collective migration of zebrafish prechordal plate cells (Dumortier et al, 2012) by controlling E-cadherin/Rac-dependent protrusion formation. Transplant experiments show that isolated prechordal plate cells are unable to migrate directionally until they make contact with the rest of the collective (Dumortier et al, 2012).…”

“…Recent work has shown that Wnt/PCP-mediated contact-dependent polarity drives collective migration of zebrafish prechordal plate cells (Dumortier et al, 2012) by controlling E-cadherin/Rac-dependent protrusion formation. Transplant experiments show that isolated prechordal plate cells are unable to migrate directionally until they make contact with the rest of the collective (Dumortier et al, 2012). Importantly, this work suggested that intrinsic directional information might arise from cell-cell interactions independently of guidance cues (Dumortier et al, 2012).…”

“…2 j; Davidson et al, 2002;Montero et al, 2003;Diz-Muñoz et al, 2010;Damm and Winklbauer, 2011;Dumortier et al, 2012;Weber et al, 2012). Similar to the neural crest, the Wnt/planar cell polarity (PCP) pathway has been suggested to contribute to orientation of protrusions and coordination of migration of mesendodermal cells (Ulrich et al, 2003;Dumortier et al, 2012).…”