The emergence of circadian timekeeping in the intestine

Kathyani Parasram, Amy Zuccato, Minjeong Shin, Reegan Willms, Brian DeVeale, Edan Foley and Phillip Karpowicz ()
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Kathyani Parasram: University of Windsor
Amy Zuccato: University of Windsor
Minjeong Shin: University of Alberta
Reegan Willms: University of Alberta
Brian DeVeale: University of Windsor
Edan Foley: University of Alberta
Phillip Karpowicz: University of Windsor

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract The circadian clock is a molecular timekeeper, present from cyanobacteria to mammals, that coordinates internal physiology with the external environment. The clock has a 24-h period however development proceeds with its own timing, raising the question of how these interact. Using the intestine of Drosophila melanogaster as a model for organ development, we track how and when the circadian clock emerges in specific cell types. We find that the circadian clock begins abruptly in the adult intestine and gradually synchronizes to the environment after intestinal development is complete. This delayed start occurs because individual cells at earlier stages lack the complete circadian clock gene network. As the intestine develops, the circadian clock is first consolidated in intestinal stem cells with changes in Ecdysone and Hnf4 signalling influencing the transcriptional activity of Clk/cyc to drive the expression of tim, Pdp1, and vri. In the mature intestine, stem cell lineage commitment transiently disrupts clock activity in differentiating progeny, mirroring early developmental clock-less transitions. Our data show that clock function and differentiation are incompatible and provide a paradigm for studying circadian clocks in development and stem cell lineages.

Date: 2024
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DOI: 10.1038/s41467-024-45942-4

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