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Ripply suppresses Tbx6 to induce dynamic-to-static conversion in somite segmentation

Authors: 
Yabe T, Uriu K, Takada S
Citation: 
Nat Commun. 2023 Apr 13;14(1):2115. doi: 10.1038/s41467-023-37745-w
Abstract: 
The metameric pattern of somites is created based on oscillatory expression of clock genes in presomitic mesoderm. However, the mechanism for converting the dynamic oscillation to a static pattern of somites is still unclear. Here, we provide evidence that Ripply/Tbx6 machinery is a key regulator of this conversion. Ripply1/Ripply2-mediated removal of Tbx6 protein defines somite boundary and also leads to cessation of clock gene expression in zebrafish embryos. On the other hand, activation of ripply1/ripply2 mRNA and protein expression is periodically regulated by clock oscillation in conjunction with an Erk signaling gradient. Whereas Ripply protein decreases rapidly in embryos, Ripply-triggered Tbx6 suppression persists long enough to complete somite boundary formation. Mathematical modeling shows that a molecular network based on results of this study can reproduce dynamic-to-static conversion in somitogenesis. Furthermore, simulations with this model suggest that sustained suppression of Tbx6 caused by Ripply is crucial in this conversion.
Epub: 
Not Epub
Organism or Cell Type: 
zebrafish
Delivery Method: 
microinjection