Actomyosin Generated Tension Coordinates Cell Movements during Early Zebrafish Development

Abstract

Coordinated cell migration is a fundamental aspect of biological processes ranging from wound healing to embryonic development. How this coordination occurs over length scales much longer than individual cells is poorly understood. We use zebrafish epiboly as a model system to investigate the biophysical underpinnings of coordinated cell migration. During epiboly the blastoderm migrates and spreads from the animal pole of the yolk to converge at the opposite, vegetal pole. At present, very little is known about how cell migration is coordinated along the length of the blastoderm margin (BM), which is ∼3 mm at its maximal circumference. We use gentle mechanical deformation to distort the normally symmetric embryo to probe the mechanisms that generate long-range intercellular coordination during epiboly. Geometric distortion causes shape-dependent alterations in the rate of BM migration and realignment of the BM and eventual anterior-posterior (AP) axis away from the initial animal-vegetal axis and toward the new long axis of the embryo. Chemical disruption of the actin band, a contractile ring of actin and myosin immediately vegetal to the BM, restores uniform migration along its length and eliminates AP axis reorientation. A quantitative model that incorporates tension generated by the actin band accounts for these observations, consistent with the idea that physical forces can generate long-range, coordinated cell movements that would be difficult to achieve by biochemical signaling alone. We hypothesize that this mechanism may provide a general means of coordinating long-range cell migration, for example during wound healing and Drosophila dorsal closure. Our data additionally suggest that AP axis specification, a fundamental step in the development of all embryos, is sensitive to mechanical cues. Taken together, these observations support the likelihood that mechanical forces may shape morphogenesis throughout development.