美国美国哈佛大学Yusuf Ilker Yaman和Sharad Ramanathan合作发现，控制人体类器官对称性的破坏揭示信号传导梯度驱动分节时钟波。相关论文于2023年1月18日在线发表在《细胞》杂志上。

为了深入了解控制人类轴向形态发生动态的信号，研究人员通过诱导来自人类多能干细胞的空间偶联上皮囊肿的前后对称破坏来生成轴向延伸类器官。每个类器官由神经管组成，两侧为体细胞前中胚层，按顺序分割为体节。体节细胞分化基因MESP2的周期性激活在空间和时间上与类器官体细胞前中胚层中向前移动的分节时钟波一致，这概括了体节发生的关键方面。时间扰动表明FGF和WNT信号在轴向伸长和体细胞发生中起着不同的作用，FGF信号梯度驱动分节时钟波。通过生成和扰动类器官，这些类器官同时概括了人类胚胎中多个轴向组织的结构，这项工作为剖析人类胚胎发生的机制提供了一种手段。

据了解，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、生长发育和神经管形成。

附：英文原文

Title: Controlling human organoid symmetry breaking reveals signaling gradients drive segmentation clock waves

Author: Yusuf Ilker Yaman, Sharad Ramanathan

Issue&Volume: 2023-01-18

Abstract: Axial development of mammals involves coordinated morphogenetic events, includingaxial elongation, somitogenesis, and neural tube formation. To gain insight into thesignals controlling the dynamics of human axial morphogenesis, we generated axiallyelongating organoids by inducing anteroposterior symmetry breaking of spatially coupledepithelial cysts derived from human pluripotent stem cells. Each organoid was composedof a neural tube flanked by presomitic mesoderm sequentially segmented into somites.Periodic activation of the somite differentiation gene MESP2 coincided in space andtime with anteriorly traveling segmentation clock waves in the presomitic mesodermof the organoids, recapitulating critical aspects of somitogenesis. Timed perturbationsdemonstrated that FGF and WNT signaling play distinct roles in axial elongation andsomitogenesis, and that FGF signaling gradients drive segmentation clock waves. Bygenerating and perturbing organoids that robustly recapitulate the architecture ofmultiple axial tissues in human embryos, this work offers a means to dissect mechanismsunderlying human embryogenesis.

DOI: 10.1016/j.cell.2022.12.042

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01585-9