RT Journal Article SR Electronic T1 Coupled organoids reveal that signaling gradients drive traveling segmentation clock waves during human axial morphogenesis JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.05.10.491359 DO 10.1101/2022.05.10.491359 A1 Yusuf Ilker Yaman A1 Roya Huang A1 Sharad Ramanathan YR 2022 UL http://biorxiv.org/content/early/2022/05/11/2022.05.10.491359.abstract AB Axial development of mammals is a dynamic process involving several coordinated morphogenetic events including axial elongation, somitogenesis, and neural tube formation. How different signals control the dynamics of human axial morphogenesis remains largely unknown. By inducing anteroposterior symmetry breaking of spatially coupled epithelial cysts derived from human pluripotent stem cells, we were able to generate hundreds of axially elongating organoids. Each organoid was composed of a neural tube flanked by presomitic mesoderm that was 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 key aspects of somitogenesis. Through timed perturbations of organoids, we demonstrated that FGF and WNT signaling play distinct roles in axial elongation and somitogenesis, and that the segmentation clock waves are driven by FGF signaling gradients. By generating and perturbing organoids that robustly recapitulate the architecture and dynamics of multiple axial tissues in human embryos, this work offers a means to dissect complex mechanisms underlying human embryogenesis.Competing Interest StatementThe authors have declared no competing interest.