BIO411H5 Lecture Notes - Lecture 1: Phase Transition, Circadian Clock, Circadian Rhythm
Document Summary
The circadian clock gates the intestinal stem cell regenerative state. The intestine contains intestinal stem cells (iscs) that has the ability to regenerate itself to replace damaged cells. It was hypothesized that circadian rhythms might have influenced the intestine s regenerative response. In the drosophila, iscs divide to produce enteroblasts (ebs) that differentiates into absorptive enterocytes (ecs) or enteroendocrine cell (ee). Researchers tested several genes after damage by dextran-sodium sulfate (dss) in the intestine. Using quantitative rt-pcr, it was found that period accumulated in the early evening and accumulated in the nucleus in the early morning, showing rhythmicity in the intestine. To further test rhythmicity, per was mutated to a viable loss-of-function mutation per01 which does not exhibit behavioral rhythmicity. Per01 isc damaged by dss had reduced mitoses at all time points. Per knockdown in either iscs or ecs also had similar results, suggesting that intestinal regeneration was regulated by per.
