RT Journal Article SR Electronic T1 Dynamically Evolving Cell Sizes During Early Development Enable Normal Gastrulation Movements In Zebrafish Embryos JF bioRxiv FD Cold Spring Harbor Laboratory SP 481325 DO 10.1101/481325 A1 Triveni Menon A1 Asfa Sabrin Borbora A1 Rahul Kumar A1 Sreelaja Nair YR 2019 UL http://biorxiv.org/content/early/2019/10/10/481325.abstract AB 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 must 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 this 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. We show that cell size reduction during early development follows power-law scaling. 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 rather than from pleotropic effects of altered ploidy. This interpretation is strengthened by the result wherein restoring cell sizes to normal diploid-like values rescues gastrulation defects. Live imaging of chimeric embryos where haploid/tetraploid cells are introduced into diploid embryos reveal the cell-autonomous nature of the migration defects. Additionally, aberrant intracellular actin dynamics with respect to the vectorial direction of motion suggests a cellular mechanism behind the migration defects. Taken together, early reductive cell divisions potentially allow dynamic, stage-specific cell size norms to emerge, which enables efficient collective cell migration to correctly position cells in space and time to shape an amorphous ball of blastoderm into an embryo.