The Adaptor Protein Lurap1 Is Required for Cell Cohesion during Epiboly Movement in Zebrafish

SIMPLE SUMMARY: Cell adhesion and active cell shape changes play an important role in morphogenetic movements during embryonic development. Zebrafish is an attractive model for the study of cellular and molecular mechanisms underlying these processes. Epiboly is a conserved gastrulation cell movement, which describes the thinning and spreading of an external sheet of cells to cover other groups of cells in the embryo. It involves differential cellular adhesive properties and dynamic cytoskeletal organization across the embryo, but how these are regulated remains elusive. We found that the adaptor protein Lurap1, which interacts with other proteins required for cell migration, plays a role in cell adhesion during epiboly. In zebrafish mutants with loss of Lurap1 function, there is a reduced cellular cohesion in the epithelial blastoderm cells and a delayed epiboly movement. Our observations suggest that Lurap1 is implicated in the regulation of cellular behavior changes for coordinated morphogenetic movements in vertebrate embryos. ABSTRACT: Cell adhesion and polarized cellular behaviors play critical roles in a wide variety of morphogenetic events. In the zebrafish embryo, epiboly represents an important process of epithelial morphogenesis that involves differential cell adhesion and dynamic cell shape changes for coordinated movements of different cell populations, but the underlying mechanism remains poorly understood. The adaptor protein Lurap1 functions to link myotonic dystrophy kinase-related Rac/Cdc42-binding kinase with MYO18A for actomyosin retrograde flow in cell migration. We previously reported that it interacts with Dishevelled in convergence and extension movements during gastrulation. Here, we show that it regulates blastoderm cell adhesion and radial cell intercalation during epiboly. In zebrafish mutant embryos with loss of both maternal and zygotic Lurap1 function, deep cell multilayer of the blastoderm exhibit delayed epiboly with respect to the superficial layer. Time-lapse imaging reveals that these deep cells undergo unstable intercalation, which impedes their expansion over the yolk cell. Cell sorting and adhesion assays indicate reduced cellular cohesion of the blastoderm. These defects are correlated with disrupted cytoskeletal organization in the cortex of blastoderm cells. Thus, the present results extend our previous works by demonstrating that Lurap1 is required for cell adhesion and cell behavior changes to coordinate cell movements during epithelial morphogenesis. They provide insights for a further understanding of the regulation of cytoskeletal organization during gastrulation cell movements.