Summary
This dissertation demonstrates that peripheral circadian oscillators couple intercellularly via secreted signaling molecules, identifying TGF-β as a key coupling factor that regulates PER2 expression and phase adjustment. Disruption of TGF-β signaling leads to desynchronization of cellular oscillators, reduced amplitude, and increased sensitivity to zeitgeber signals, with implications for circadian health and rhythmic organ function.
Key Findings
- TGF-β was identified as a peripheral intercellular coupling factor for circadian oscillators in non-SCN tissues.
- TGF-β induces both cAMP enhancer motif-dependent and immediate early expression of the clock gene PER2, thereby regulating phase adjustment of molecular circadian oscillations.
- Genetic and pharmacological disruption of TGF-β signaling caused desynchronization of cellular oscillators, manifesting as reduced oscillation amplitude and increased sensitivity to zeitgeber signals.
Categories
Sleep & Circadian Health: Investigates intercellular coupling mechanisms of peripheral circadian oscillators and their role in maintaining circadian synchrony.
The Science of Light: Identifies TGF-β as a molecular coupling factor regulating phase adjustment of circadian oscillations, advancing understanding of oscillator network biology.
Author(s)
AM Finger
Publication Year
2020
Related Publications
Sleep & Circadian Health
- Phototransduction by retinal ganglion cells that set the circadian clock
- The mammalian circadian timing system: organization and coordination of central and peripheral clocks
- The two‐process model of sleep regulation: a reappraisal
- Melanopsin is required for non-image-forming photic responses in blind mice
- Strange vision: ganglion cells as circadian photoreceptors
The Science of Light
- Phototransduction by retinal ganglion cells that set the circadian clock
- Color appearance models
- The mammalian circadian timing system: organization and coordination of central and peripheral clocks
- Diminished pupillary light reflex at high irradiances in melanopsin-knockout mice
- Melanopsin is required for non-image-forming photic responses in blind mice