Supracellular organization confers directionality and mechanical potency to migrating pairs of cardiopharyngeal progenitor cells.

Yelena Y Bernadskaya,Haicen Yue,Alex Mogilner,Calina Copos,Lionel Christiaen

doi:10.7554/elife.70977

Abstract

Physiological and pathological morphogenetic events involve a wide array of collective movements, suggesting that multicellular arrangements confer biochemical and biomechanical properties contributing to tissue-scale organization. The Ciona cardiopharyngeal progenitors provide the simplest model of collective cell migration, with cohesive bilateral cell pairs polarized along the leader-trailer migration path while moving between the ventral epidermis and trunk endoderm. We use the Cellular Potts Model to computationally probe the distributions of forces consistent with shapes and collective polarity of migrating cell pairs. Combining computational modeling, confocal microscopy, and molecular perturbations, we identify cardiopharyngeal progenitors as the simplest cell collective maintaining supracellular polarity with differential distributions of protrusive forces, cell-matrix adhesion, and myosin-based retraction forces along the leader-trailer axis. 4D simulations and experimental observations suggest that cell-cell communication helps establish a hierarchy to align collective polarity with the direction of migration, as observed with three or more cells in silico and in vivo. Our approach reveals emerging properties of the migrating collective: cell pairs are more persistent, migrating longer distances, and presumably with higher accuracy. Simulations suggest that cell pairs can overcome mechanical resistance of the trunk endoderm more effectively when they are polarized collectively. We propose that polarized supracellular organization of cardiopharyngeal progenitors confers emergent physical properties that determine mechanical interactions with their environment during morphogenesis.

Highlights

Cell migration is a fundamental cellular behavior involved in developmental and physiological processes including germline, craniofacial, and cardiac development, angiogenesis and wound healing, and pathogenesis such as cancer metastasis[1, 2]
Many developmental, homeostatic, and pathogenic morphogenetic events involve the coordinated movements of cellular collectives, as observed during neural crest migration in chick, lateral line migration in zebrafish, and border cell migration in the Drosophila ovary[4 5, 6]
Leader cells typically adopt splayed morphologies with protrusive activity at the leading edge, while trailing cells display a tapered rear[38]. This organization is conspicuous in pairs of multipotent cardiopharyngeal progenitor cells in the embryo of the tunicate Ciona

Summary

Introduction

Cell migration is a fundamental cellular behavior involved in developmental and physiological processes including germline, craniofacial, and cardiac development, angiogenesis and wound healing, and pathogenesis such as cancer metastasis[1, 2]. In complex dynamic multicellular environments, cells integrate biochemical and mechanical cues to guide their migration. Like neutrophils, navigate complex environments as single cells[3]. Many developmental, homeostatic, and pathogenic morphogenetic events involve the coordinated movements of cellular collectives, as observed during neural crest migration in chick, lateral line migration in zebrafish, and border cell migration in the Drosophila ovary[4 5, 6]. The properties that emerge from collective organization are thought to facilitate biochemical and mechanical integration and foster efficient and accurate tissue morphogenesis in a multicellular context 7-11. Individual cells move as autonomous units, while adjusting directionality and speed relative to their neighbors[14]

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Conclusion