GSE158023
Dynamic Optima In Cell Sizes Enable Normal Gastrulation Movements In Zebrafish Embryos During Early Development
Current knowledge of the mechanisms of cell migration is based on differentiated cells in culture where it is known that the actomyosin machinery drives migration via dynamic interactions with the extracellular matrix and adhesion complexes. However, unlike differentiated cells, cells in early metazoan embryos also dynamically change cell sizes as they migrate. The relevance of cell size to cell migration and embryonic development is not known. Here we investigate these phenomena in zebrafish embryos, a model system in which reductive cell divisions causes cell sizes to decrease naturally over time as cells migrate collectively to sculpt the embryonic body plan. Because mutations that can perturb cell sizes so early in development do not exist, we generate haploid and tetraploid zebrafish embryos and show that cell sizes in such embryos are smaller and larger than the diploid norm, respectively. Cells in embryos made of smaller or larger than normal cells migrate sub-optimally, leading to gastrulation defects. Multiple lines of evidence suggest that the observed defects originate from altered cell size, and not from pleotropic effects of altered ploidy. This interpretation is strengthened by finding that gastrulation defects are rescued by increasing cell sizes in embryos wherein cell sizes are smaller than normal. We show that the migration defects are cell-autonomous by live imaging migrating haploid and tetraploid cells during gastrulation in chimeric diploid embryos. Analysis of membrane protrusion dynamics in single cells shows that cells normally extend protrusions non-uniformly during migration, a phenomenon which is perturbed when cell sizes deviate from the norm. Thus, an optimal range of developmental stage-specific cell sizes appears necessary for collective cell migration to correctly position cells in space and time to shape an amorphous ball of blastoderm into an embryo. Overall design: RNA sequencing analysis of diploid (control), haploid and tetraploid zebrafish embryos at 3 hours post fertilization (hpf) stage done as 3 experimental replicates for each condition