Cell 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.

细胞迁移是形成胃祖细胞的进化保守过程的主要驱动力，它形成了后生动物的胚胎形态。尽管进行了充分的研究，但胃气化过程中细胞迁移的分子和细胞机制缺乏对细胞大小对集体细胞迁移的贡献的了解。这在后生动物发育的早期阶段尤其重要，后生动物的发育主要由不断变化的细胞大小主导，而后代细胞大量迁移塑造胚胎。在这里，我们研究斑马鱼胚胎中的这种现象，这是一个模型系统，其中早期细胞分裂会导致细胞大小随着时间的推移自然减小，因为细胞会共同迁移以雕刻出胚胎的身体计划。由于不存在可以扰乱细胞大小的突变，因此我们产生了单倍体和四倍体斑马鱼胚胎，并表明这些胚胎中的细胞大小分别比二倍体标准小和大。由比正常细胞小的或更大的胚胎中的细胞亚最佳迁移，导致胃形成缺陷。基因表达分析表明，观察到的缺陷源自改变的细胞大小，而不是源自倍性改变的多效性效应。当通过增加胚胎的细胞大小（其中细胞大小小于正常大小）来挽救胃泌尿缺陷时，这种解释会得到加强。我们表明，通过在嵌合二倍体胚胎的胃形成过程中进行单倍体和四倍体细胞的实时成像迁移，迁移缺陷是细胞自治的。对单个细胞中膜突起动态的分析表明，细胞通常在迁移过程中不均匀地延伸突起，这种现象在细胞大小偏离正常值时会受到干扰。因此，最佳的发育阶段特异性细胞大小范围对于集体细胞迁移以正确地将细胞在空间和时间上定位以将胚盘的无定形球塑造成胚胎是必要的。我们表明，通过在嵌合二倍体胚胎的胃形成过程中进行单倍体和四倍体细胞的实时成像迁移，迁移缺陷是细胞自治的。对单个细胞中膜突起动态的分析表明，细胞通常在迁移过程中不均匀地延伸突起，这种现象在细胞大小偏离正常值时会受到干扰。因此，最佳的发育阶段特异性细胞大小范围对于集体细胞迁移以正确地将细胞在空间和时间上定位以将胚盘的无定形球塑造成胚胎是必要的。我们显示，通过在嵌合二倍体胚胎的胃形成过程中通过实时成像迁移单倍体和四倍体细胞，迁移缺陷是细胞自治的。对单个细胞中膜突起动态的分析表明，细胞通常在迁移过程中不均匀地延伸突起，这种现象在细胞大小偏离正常值时会受到干扰。因此，最佳的发育阶段特异性细胞大小范围对于集体细胞迁移以正确地将细胞在空间和时间上定位以将胚盘的无定形球塑造成胚胎是必要的。