Matsuda, MitsuhiroHayashi, HanakoGarcía Ojalvo, JordiYoshioka-Kobayashi, KumikoKageyama, RyoichiroYamanaka, YoshihiroIkeya, MakotoToguchida, JunyaAlev, CantasEbisuya, Miki2022-01-262022-01-262020Matsuda M, Hayashi H, Garcia-Ojalvo J, Yoshioka-Kobayashi K, Kageyama R, Yamanaka Y, Ikeya M, Toguchida J, Alev C, Ebisuya M. Species-specific segmentation clock periods are due to differential biochemical reaction speeds. Science. 2020;369(6510):1450-5. DOI: 10.1126/science.aba76680036-8075http://hdl.handle.net/10230/52326Although mechanisms of embryonic development are similar between mice and humans, the time scale is generally slower in humans. To investigate these interspecies differences in development, we recapitulate murine and human segmentation clocks that display 2- to 3-hour and 5- to 6-hour oscillation periods, respectively. Our interspecies genome-swapping analyses indicate that the period difference is not due to sequence differences in the HES7 locus, the core gene of the segmentation clock. Instead, we demonstrate that multiple biochemical reactions of HES7, including the degradation and expression delays, are slower in human cells than they are in mouse cells. With the measured biochemical parameters, our mathematical model accounts for the two- to threefold period difference between the species. We propose that cell-autonomous differences in biochemical reaction speeds underlie temporal differences in development between species.application/pdfengThis is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Matsuda M, Hayashi H, Garcia-Ojalvo J, Yoshioka-Kobayashi K, Kageyama R, Yamanaka Y, Ikeya M, Toguchida J, Alev C, Ebisuya M. Species-specific segmentation clock periods are due to differential biochemical reaction speeds. Science. 2020;369(6510):1450-5. DOI: 10.1126/science.aba7668info:eu-repo/semantics/articlehttp://dx.doi.org/10.1126/science.aba7668info:eu-repo/semantics/openAccess