Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA; The Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
The Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
Curr Biol. 2023 Aug 21;33(16):3536-3543.e6. doi: 10.1016/j.cub.2023.07.050. Epub 2023 Aug 9.
Bilateral symmetry defines much of the animal kingdom and is crucial for numerous functions of bilaterian organisms. Genetic approaches have discovered highly conserved patterning networks that establish bilateral symmetry in early embryos, but how this symmetry is maintained throughout subsequent morphogenetic events remains largely unknown. Here we show that the terminal patterning system-which relies on Ras/ERK signaling through activation of the Torso receptor by its ligand Trunk-is critical for preserving bilateral symmetry during Drosophila body axis elongation, a process driven by cell rearrangements in the two identical lateral regions of the embryo and specified by the dorsal-ventral and anterior-posterior patterning systems. We demonstrate that fluctuating asymmetries in this rapid convergent-extension process are attenuated in normal embryos over time, possibly through noise-dissipating forces from the posterior midgut invagination and movement. However, when Torso signaling is attenuated via mutation of Trunk or RNAi directed against downstream Ras/ERK pathway components, body axis elongation results in a characteristic corkscrew phenotype, which reflects dramatic reorganization of global tissue flow and is incompatible with viability. Our results reveal a new function downstream of the Drosophila terminal patterning system in potentially active control of bilateral symmetry and should motivate systematic search for similar symmetry-preserving regulatory mechanisms in other bilaterians.
双侧对称定义了动物界的大部分内容，对于两侧对称生物的众多功能至关重要。遗传方法已经发现了高度保守的模式形成网络，这些网络在早期胚胎中建立了双侧对称，但这种对称性如何在随后的形态发生事件中保持仍然很大程度上未知。在这里，我们表明，终端模式系统 - 依赖于 Ras/ERK 信号，通过其配体 Trunk 激活 Torso 受体 - 对于在果蝇体轴伸长过程中保持双侧对称至关重要，这个过程是由胚胎两个相同的侧区域中的细胞重排驱动的，并由背腹和前后模式系统指定。我们证明，在正常胚胎中，这个快速收敛-延伸过程中的波动不对称性随着时间的推移而减弱，这可能是通过后中肠内陷和运动的耗散力。然而，当通过突变 Trunk 或针对下游 Ras/ERK 途径成分的 RNAi 来减弱 Torso 信号时，体轴伸长会导致特征性的螺旋形表型，这反映了全局组织流的剧烈重组，并且与生存能力不兼容。我们的结果揭示了果蝇终端模式系统下游的一个新功能，可能在积极控制双侧对称方面具有重要作用，这应该促使人们在其他两侧对称生物中系统地寻找类似的对称保护调节机制。
