类有机物
生物
延伸率
细胞生物学
Wnt信号通路
胚胎
解剖
极性(国际关系)
轴对称性
联轴节(管道)
信号转导
物理
遗传学
机械工程
量子力学
极限抗拉强度
工程类
冶金
材料科学
细胞
作者
Giridhar M. Anand,Heitor C. Megale,Sean H. Murphy,Theresa Weis,Zuwan Lin,Yichun He,Xiao Wang,Jia Liu,Sharad Ramanathan
出处
期刊:Cell
[Elsevier]
日期:2023-02-01
卷期号:186 (3): 497-512.e23
被引量:19
标识
DOI:10.1016/j.cell.2022.12.043
摘要
The human embryo breaks symmetry to form the anterior-posterior axis of the body. As the embryo elongates along this axis, progenitors in the tail bud give rise to tissues that generate spinal cord, skeleton, and musculature. This raises the question of how the embryo achieves axial elongation and patterning. While ethics necessitate in vitro studies, the variability of organoid systems has hindered mechanistic insights. Here, we developed a bioengineering and machine learning framework that optimizes organoid symmetry breaking by tuning their spatial coupling. This framework enabled reproducible generation of axially elongating organoids, each possessing a tail bud and neural tube. We discovered that an excitable system composed of WNT/FGF signaling drives elongation by inducing a neuromesodermal progenitor-like signaling center. We discovered that instabilities in the excitable system are suppressed by secreted WNT inhibitors. Absence of these inhibitors led to ectopic tail buds and branches. Our results identify mechanisms governing stable human axial elongation.
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