|ZFIN ID: ZDB-PUB-201002-78|
Dynamic optima in cell sizes during early development enable normal gastrulation in zebrafish embryos
Menon, T., Borbora, A.S., Kumar, R., Nair, S.
|Source:||Developmental Biology 468(1-2): 26-40 (Journal)|
|Registered Authors:||Nair, Sreelaja|
|Keywords:||Cell migration, Cell size, Gastrulation, Zebrafish|
|PubMed:||32937161 Full text @ Dev. Biol.|
Menon, T., Borbora, A.S., Kumar, R., Nair, S. (2020) Dynamic optima in cell sizes during early development enable normal gastrulation in zebrafish embryos. Developmental Biology. 468(1-2):26-40.
ABSTRACTCell migration is the main driver of the evolutionarily conserved process of gastrulation, which shapes metazoan embryo morphology. The molecular and cellular mechanisms of cell migration during gastrulation though well researched lacks an understanding of the contribution of cell sizes to collective cell migration. This is especially important during the early phase of metazoan development, which is dominated by constantly changing cell sizes in the background of which cells migrate en mass to shape the embryo. Here we investigate this phenomenon in zebrafish embryos, a model system in which early 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. Gene expression analysis suggests that the observed defects originate from altered cell size, and not from pleiotropic effects of altered ploidy. This interpretation is strengthened when 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.