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Controlling human organoid symmetry breaking reveals signaling gradients drive segmentation clock waves
Cell ( IF 64.5 ) Pub Date : 2023-01-18 , DOI: 10.1016/j.cell.2022.12.042
Yusuf Ilker Yaman 1 , Sharad Ramanathan 2
Affiliation  

Axial development of mammals involves coordinated morphogenetic events, including axial elongation, somitogenesis, and neural tube formation. To gain insight into the signals controlling the dynamics of human axial morphogenesis, we generated axially elongating organoids by inducing anteroposterior symmetry breaking of spatially coupled epithelial cysts derived from human pluripotent stem cells. Each organoid was composed of a neural tube flanked by presomitic mesoderm sequentially segmented into somites. Periodic activation of the somite differentiation gene MESP2 coincided in space and time with anteriorly traveling segmentation clock waves in the presomitic mesoderm of the organoids, recapitulating critical aspects of somitogenesis. Timed perturbations demonstrated that FGF and WNT signaling play distinct roles in axial elongation and somitogenesis, and that FGF signaling gradients drive segmentation clock waves. By generating and perturbing organoids that robustly recapitulate the architecture of multiple axial tissues in human embryos, this work offers a means to dissect mechanisms underlying human embryogenesis.



中文翻译:

控制人体类器官对称性破缺揭示信号梯度驱动分割时钟波

哺乳动物的轴向发​​育涉及协调的形态发生事件,包括轴向伸长、体细胞发生和神经管形成。为了深入了解控制人类轴向形态发生动力学的信号,我们通过诱导源自人类多能干细胞的空间耦合上皮囊肿的前后对称性破坏来生成轴向伸长的类器官。每个类器官都由一个神经管组成,神经管的两侧是生前中胚层,这些中胚层依次被分割成体节。体细胞分化基因 MESP2 的周期性激活在空间和时间上与类器官的前体中胚层中的前向行进分割时钟波一致,概括了体细胞发生的关键方面。定时扰动表明 FGF 和 WNT 信号在轴向伸长和体细胞发生中发挥着不同的作用,并且 FGF 信号梯度驱动分段时钟波。通过生成和扰动能够有力地概括人类胚胎中多个轴组织结构的类器官,这项工作提供了一种剖析人类胚胎发生机制的方法。

更新日期:2023-01-18
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