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

Area of Science:

• Developmental Biology
• Chronobiology
• Molecular Biology

Background:

• Mammalian embryonic development involves precise temporal regulation, with circadian clocks emerging late.
• Early development relies on the segmentation clock for body plan formation in the posterior presomitic mesoderm.
• Circadian regulators like CLOCK/BMAL1 are suppressed during early embryonic stages.

Purpose of the Study:

• To investigate the interaction between circadian clock components (CLOCK/BMAL1) and the segmentation clock.
• To determine the effect of CLOCK/BMAL1 on the segmentation clock's Hes7 oscillation.
• To understand the implications of premature CLOCK/BMAL1 expression on embryonic development.

Main Methods:

• Utilizing induced posterior presomitic mesoderm (iPSM) and gastruloids.
• Analyzing Hes7 oscillation in the presence of functional CLOCK/BMAL1.
• Performing RNA sequencing to assess transcriptional changes.

Main Results:

• Functional CLOCK/BMAL1 severely interferes with the ultradian rhythm of the segmentation clock.
• Premature CLOCK/BMAL1 expression disrupts Hes7 transcription and its regulatory pathways.
• These disruptions were observed in both induced PSM and gastruloid models.

Conclusions:

• Suppression of CLOCK/BMAL1-mediated transcription is crucial for intact mammalian somitogenesis.
• The segmentation clock's rhythm is sensitive to the early presence of circadian regulators.
• This suggests a necessary temporal separation between circadian clock establishment and early body plan formation.