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Circadian key component CLOCK/BMAL1 interferes with segmentation clock in mouse embryonic organoids

In mammals, circadian clocks are strictly suppressed during early embryonic stages, as well as in pluripotent stem cells, by the lack of CLOCK/BMAL1-mediated circadian feedback loops. During ontogenesis, the innate circadian clocks emerge gradually at a late developmental stage, and with these, the...

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Autores principales: Umemura, Yasuhiro, Koike, Nobuya, Tsuchiya, Yoshiki, Watanabe, Hitomi, Kondoh, Gen, Kageyama, Ryoichiro, Yagita, Kazuhiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8746294/
https://www.ncbi.nlm.nih.gov/pubmed/34930826
http://dx.doi.org/10.1073/pnas.2114083119
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author Umemura, Yasuhiro
Koike, Nobuya
Tsuchiya, Yoshiki
Watanabe, Hitomi
Kondoh, Gen
Kageyama, Ryoichiro
Yagita, Kazuhiro
author_facet Umemura, Yasuhiro
Koike, Nobuya
Tsuchiya, Yoshiki
Watanabe, Hitomi
Kondoh, Gen
Kageyama, Ryoichiro
Yagita, Kazuhiro
author_sort Umemura, Yasuhiro
collection PubMed
description In mammals, circadian clocks are strictly suppressed during early embryonic stages, as well as in pluripotent stem cells, by the lack of CLOCK/BMAL1-mediated circadian feedback loops. During ontogenesis, the innate circadian clocks emerge gradually at a late developmental stage, and with these, the circadian temporal order is invested in each cell level throughout a body. Meanwhile, in the early developmental stage, a segmented body plan is essential for an intact developmental process, and somitogenesis is controlled by another cell-autonomous oscillator, the segmentation clock, in the posterior presomitic mesoderm (PSM). In the present study, focusing upon the interaction between circadian key components and the segmentation clock, we investigated the effect of the CLOCK/BMAL1 on the segmentation clock Hes7 oscillation, revealing that the expression of functional CLOCK/BMAL1 severely interferes with the ultradian rhythm of segmentation clock in induced PSM and gastruloids. RNA sequencing analysis implied that the premature expression of CLOCK/BMAL1 affects the Hes7 transcription and its regulatory pathways. These results suggest that the suppression of CLOCK/BMAL1-mediated transcriptional regulation during the somitogenesis may be inevitable for intact mammalian development.
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spelling pubmed-87462942022-01-25 Circadian key component CLOCK/BMAL1 interferes with segmentation clock in mouse embryonic organoids Umemura, Yasuhiro Koike, Nobuya Tsuchiya, Yoshiki Watanabe, Hitomi Kondoh, Gen Kageyama, Ryoichiro Yagita, Kazuhiro Proc Natl Acad Sci U S A Biological Sciences In mammals, circadian clocks are strictly suppressed during early embryonic stages, as well as in pluripotent stem cells, by the lack of CLOCK/BMAL1-mediated circadian feedback loops. During ontogenesis, the innate circadian clocks emerge gradually at a late developmental stage, and with these, the circadian temporal order is invested in each cell level throughout a body. Meanwhile, in the early developmental stage, a segmented body plan is essential for an intact developmental process, and somitogenesis is controlled by another cell-autonomous oscillator, the segmentation clock, in the posterior presomitic mesoderm (PSM). In the present study, focusing upon the interaction between circadian key components and the segmentation clock, we investigated the effect of the CLOCK/BMAL1 on the segmentation clock Hes7 oscillation, revealing that the expression of functional CLOCK/BMAL1 severely interferes with the ultradian rhythm of segmentation clock in induced PSM and gastruloids. RNA sequencing analysis implied that the premature expression of CLOCK/BMAL1 affects the Hes7 transcription and its regulatory pathways. These results suggest that the suppression of CLOCK/BMAL1-mediated transcriptional regulation during the somitogenesis may be inevitable for intact mammalian development. National Academy of Sciences 2021-12-20 2022-01-04 /pmc/articles/PMC8746294/ /pubmed/34930826 http://dx.doi.org/10.1073/pnas.2114083119 Text en Copyright © 2021 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Umemura, Yasuhiro
Koike, Nobuya
Tsuchiya, Yoshiki
Watanabe, Hitomi
Kondoh, Gen
Kageyama, Ryoichiro
Yagita, Kazuhiro
Circadian key component CLOCK/BMAL1 interferes with segmentation clock in mouse embryonic organoids
title Circadian key component CLOCK/BMAL1 interferes with segmentation clock in mouse embryonic organoids
title_full Circadian key component CLOCK/BMAL1 interferes with segmentation clock in mouse embryonic organoids
title_fullStr Circadian key component CLOCK/BMAL1 interferes with segmentation clock in mouse embryonic organoids
title_full_unstemmed Circadian key component CLOCK/BMAL1 interferes with segmentation clock in mouse embryonic organoids
title_short Circadian key component CLOCK/BMAL1 interferes with segmentation clock in mouse embryonic organoids
title_sort circadian key component clock/bmal1 interferes with segmentation clock in mouse embryonic organoids
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8746294/
https://www.ncbi.nlm.nih.gov/pubmed/34930826
http://dx.doi.org/10.1073/pnas.2114083119
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