Cell size heterogeneity early in development is required for collective cell migration during gastrulation in zebrafish
AbstractMetazoan embryos begin life as a single large cell, which divides to generate an entire multicellular organism. This natural progression is characterized by an early, visually striking phenomenon of progressive reduction in cell size, since early cell divisions occur in the absence of cell growth. It is intuitive that early embryogenesis, wherein the phenomenon of growing numbers of progressively smaller cells dominate, cell size may be an important factor for normal development.
... development. However, in the absence of experimental efforts directed at altering cell sizes in early embryos, the importance of optimal cell sizes early in development for normal embryogenesis remains an intuitive conjecture at best. We used haploid and tetraploid zebrafish as tools to obtain embryos with smaller or larger than the normal diploid size cells, respectively. Analysis of early development in haploids and tetraploids revealed that when reductive early cell divisions generate a pool of smaller or larger cells in comparison to diploid embryos, embryonic patterning is perturbed due to defective collective migration of cells during gastrulation. During this early phase, the transcriptome of haploid and tetraploid embryos remained largely unperturbed, suggesting that the developmental defects cannot be explained by potential transcriptional changes in response to deviation from a diploid state of the genome. We additionally show that a short exposure to a combination of Aphidicolin and Hydroxyurea during blastoderm stages increases cell sizes in diploid embryos. Such embryos displayed morphological abnormalities that resembled haploid and tetraploid embryos at the end of gastrulation. Conversely, a similar short exposure to a combination of Aphidicolin and Hydroxyurea increased cell sizes in haploid embryos, partially restoring normal patterning. We posit that early reductive divisions set up an optimum range and proportions of cell sizes in early embryos onto which molecular controls are overlaid to execute collective cell migration during gastrulation. Perturbation of the normal cell size landscape triggers aberrant cell migration and gastrulation defects despite normal expression of conserved genes, revealing the importance of optimal cell sizes per se in normal embryonic patterning.