Roby Nicolas, Rauzi Matteo
Université Côte d'Azur, CNRS, Inserm, iBV, Nice, France.
Nat Commun. 2025 Feb 12;16(1):1587. doi: 10.1038/s41467-025-56880-0.
Tissue morphogenesis shapes epithelial sheets via cell remodelling to form functional living organisms. While the mechanisms underlying single morphogenetic events are well studied, how one tissue undergoes multiple concomitant shape changes remains largely unexplored. To tackle this, we study the process of simultaneous mesoderm folding and extension in the gastrulating Drosophila embryo. This composite transformation relies on a sharply timed reorganization of the cortical actomyosin network into two distinct subcellular tiers to drive concomitant cell apical constriction and lateral intercalation for tissue folding and convergence-extension, respectively. Here we elucidate the spatio-temporal control of the two-tiered actomyosin network. We show that, within the geometric constraints imposed by the columnar shape of mesoderm epithelial cells, the nucleus acts as a barrier shielding the lateral cortex from interactions with the microtubule network, thereby regulating the distribution of the key signalling molecule RhoGEF2. The relocation of the nucleus, driven by the contraction of the first actomyosin tier and the resulting cytoplasmic flow, unshields the lateral cortex for RhoGEF2 delivery to direct the stereotypic formation of the second tier. Thus, the nucleus and its position function as a spatio-temporal cytoskeleton compartmentalizer establishing a modular scaffold powering multiple simultaneous cell remodeling for composite morphogenesis.
组织形态发生通过细胞重塑塑造上皮层,从而形成功能完备的生物体。虽然单个形态发生事件的潜在机制已得到充分研究,但一个组织如何经历多种同时发生的形状变化在很大程度上仍未被探索。为了解决这个问题,我们研究了果蝇胚胎原肠胚形成过程中中胚层同时发生的折叠和延伸过程。这种复合转变依赖于皮质肌动球蛋白网络在精确的时间内重组为两个不同的亚细胞层,分别驱动伴随的细胞顶端收缩和侧向插入,以实现组织折叠和趋同延伸。在这里,我们阐明了两层肌动球蛋白网络的时空控制机制。我们发现,在中胚层上皮细胞柱状形状所施加的几何限制内,细胞核充当屏障,保护外侧皮质免受与微管网络的相互作用,从而调节关键信号分子RhoGEF2的分布。由第一层肌动球蛋白收缩和由此产生的细胞质流动驱动的细胞核重新定位,使外侧皮质暴露,以便RhoGEF2传递,从而指导第二层的定型形成。因此,细胞核及其位置起到了时空细胞骨架分隔器的作用,建立了一个模块化支架,为复合形态发生提供动力,实现多个细胞同时重塑。