scholarly journals CLOCK/BMAL1 interferes with segmentation clock oscillation in mouse embryonic organoids

2020 ◽  
Author(s):  
Yasuhiro Umemura ◽  
Nobuya Koike ◽  
Yoshiki Tsuchiya ◽  
Hitomi Watanabe ◽  
Gen Kondoh ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Clock Gene ◽  
Developmental Process ◽  
Biological Significance ◽  
Sequencing Analysis ◽  
Mammalian Development ◽  
Segmentation Clock ◽  
Interest Statement ◽  
Competing Interest ◽  
Clear Information

AbstractIn the mammalian developmental process, the segmentation clock and circadian clock appear sequentially in the embryo. However, there is no clear information about the biological significance of the mutual exclusiveness of these rhythms. Here we show that excess of the circadian components CLOCK/BMAL1 in mouse embryonic organoids, induced presomitic mesoderm and gastruloids, disrupts the Hes7 ultradian rhythm and somitogenesis. RNA sequencing analysis showed that CLOCK/BMAL1 activates the signaling pathways regulating Hes7. After establishment of the circadian clock, the expression of endogenous Hes7 and another segmentation clock gene, Lfng, tended to fluctuate with a circadian period, implying that the circadian clock potentially interferes with the segmentation clock. These results suggest that strict timing regulation of the emergence of circadian clock oscillation is essential for mammalian development.Competing Interest StatementThe authors have declared no competing interest.

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

2021 ◽  
Vol 119 (1) ◽  
pp. e2114083119
Author(s):  
Yasuhiro Umemura ◽  
Nobuya Koike ◽  
Yoshiki Tsuchiya ◽  
Hitomi Watanabe ◽  
Gen Kondoh ◽  
...  
Keyword(s):  
Developmental Stage ◽  
Developmental Process ◽  
Circadian Clocks ◽  
Early Developmental Stage ◽  
Sequencing Analysis ◽  
Mammalian Development ◽  
Segmentation Clock ◽  
Regulatory Pathways ◽  
Late Developmental Stage ◽  
Early Developmental

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.

scholarly journals Involvement of posttranscriptional regulation of Clock in the emergence of circadian clock oscillation during mouse development

2017 ◽  
Vol 114 (36) ◽  
pp. E7479-E7488 ◽  
Author(s):  
Yasuhiro Umemura ◽  
Nobuya Koike ◽  
Munehiro Ohashi ◽  
Yoshiki Tsuchiya ◽  
Qing Jun Meng ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Posttranscriptional Regulation ◽  
Cellular Differentiation ◽  
Developmental Stages ◽  
Embryonic Stem ◽  
Sequencing Analysis ◽  
Mammalian Development ◽  
Mouse Development ◽  
Circadian Genes ◽  
Clock Protein

Circadian clock oscillation emerges in mouse embryo in the later developmental stages. Although circadian clock development is closely correlated with cellular differentiation, the mechanisms of its emergence during mammalian development are not well understood. Here, we demonstrate an essential role of the posttranscriptional regulation of Clock subsequent to the cellular differentiation for the emergence of circadian clock oscillation in mouse fetal hearts and mouse embryonic stem cells (ESCs). In mouse fetal hearts, no apparent oscillation of cell-autonomous molecular clock was detectable around E10, whereas oscillation was clearly visible in E18 hearts. Temporal RNA-sequencing analysis using mouse fetal hearts reveals many fewer rhythmic genes in E10–12 hearts (63, no core circadian genes) than in E17–19 hearts (483 genes), suggesting the lack of functional circadian transcriptional/translational feedback loops (TTFLs) of core circadian genes in E10 mouse fetal hearts. In both ESCs and E10 embryos, CLOCK protein was absent despite the expression of Clock mRNA, which we showed was due to Dicer/Dgcr8-dependent translational suppression of CLOCK. The CLOCK protein is required for the discernible molecular oscillation in differentiated cells, and the posttranscriptional regulation of Clock plays a role in setting the timing for the emergence of the circadian clock oscillation during mammalian development.

scholarly journals A Functional Connection between the Circadian Clock and Hormonal Timing in Arabidopsis

Genes ◽  
2018 ◽  
Vol 9 (12) ◽  
pp. 567 ◽  
Author(s):  
Manjul Singh ◽  
Paloma Mas
Keyword(s):  
Circadian Clock ◽  
Biological Significance ◽  
Feedback Regulation ◽  
Environmental Cues ◽  
Hormone Signaling ◽  
Functional Connection ◽  
The Earth ◽  
Exogenous Cues ◽  
Rotation Of The Earth ◽  
Molecular Components

The rotation of the Earth entails changes in environmental conditions that pervasively influence an organism’s physiology and metabolism. An internal cellular mechanism known as the circadian clock acts as an internal timekeeper that is able to perceive the changes in environmental cues to generate 24-h rhythms in synchronization with daily and seasonal fluctuations. In plants, the circadian clock function is particularly important and regulates nearly every aspect of plant growth and development as well as proper responses to stresses. The circadian clock does not function in isolation but rather interconnects with an intricate network of different pathways, including those of phytohormones. Here, we describe the interplay of the circadian clock with a subset of hormones in Arabidopsis. The molecular components directly connecting the circadian and hormone pathways are described, highlighting the biological significance of such connections in the control of growth, development, fitness, and survival. We focus on the overlapping as well as contrasting circadian and hormonal functions that together provide a glimpse on how the Arabidopsis circadian system regulates hormone function in response to endogenous and exogenous cues. Examples of feedback regulation from hormone signaling to the clock are also discussed.

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