Fiuza Ulla-Maj, Bonavia Sara, Pascual-Mas Pau, Torregrosa-Cortés Gabriel, Casaní-Galdón Pablo, Robertson Gaëlle, Dias André, Martinez Arias Alfonso
Department of Medicine and Life Sciences, University Pompeu Fabra, Barcelona 08003, Spain.
Department of Medicine and Life Sciences, University Pompeu Fabra, Barcelona 08003, Spain.
Cells Dev. 2025 Aug 21;183:204043. doi: 10.1016/j.cdev.2025.204043.
Mammalian embryonic size is tightly controlled with checkpoints and compensatory mechanisms correcting size defects. Here, we take advantage of gastruloids, a stem cell embryoid system not subject to most size controls, to study the role of size in emergent properties of mammalian embryogenesis. We report that gastruloids exhibit robust morphology and transcriptional profiles within a size range. However, size affects the dynamics, and, outside a range of robust morphogenesis, the precision of anterior-posterior (AP) axial elongation. Gastruloid axial elongation exhibits active cellular contractility, requires planar cell polarity (PCP), adhesion and cell-cell contact remodelling. Smaller gastruloids initiate elongation earlier, correlated with an earlier Brachyury polarisation. Brachyury expression increases tissue fluidity. Axis formation is regulated by the balance of Brachyury multifoci coalescence and the timing of initiation of the elongation programme. Sizes beyond the robust range can modify relative tissue composition. Very small aggregates have increased neural fate bias, accompanied by a loss of paraxial mesoderm mediated by differences in Nodal signalling activity.
哺乳动物胚胎大小受到检查点和补偿机制的严格控制，这些机制可纠正大小缺陷。在这里，我们利用类原肠胚，一种不受大多数大小控制的干细胞胚状体系统，来研究大小在哺乳动物胚胎发生的新兴特性中的作用。我们报告说，类原肠胚在一定大小范围内表现出强大的形态和转录谱。然而，大小会影响动态变化，并且在强大形态发生范围之外，会影响前后（AP）轴伸长的精度。类原肠胚轴伸长表现出活跃的细胞收缩性，需要平面细胞极性（PCP）、黏附以及细胞-细胞接触重塑。较小的类原肠胚更早开始伸长，这与更早的短尾蛋白极化相关。短尾蛋白表达增加了组织流动性。轴的形成受短尾蛋白多焦点合并的平衡和伸长程序启动时间的调节。超出强大范围的大小会改变相对组织组成。非常小的聚集体具有增加的神经命运偏向，同时伴随着由节点信号活性差异介导的近轴中胚层的丧失。
