Modeling Reveals a Key Mechanism for Light-Dependent Phase Shifts of Neurospora Circadian Rhythms

Light shifts and synchronizes the phase of the circadian clock to daily environments, which is critical for maintaining the daily activities of an organism. It has been proposed that such light-dependent phase shifts are triggered by light-induced upregulation of a negative element of the core circadian clock (i.e., frq, Per1/2) in many organisms, including fungi. However, we find, using systematic mathematical modeling of the Neurospora crassa circadian clock, that the upregulation of the frq gene expression alone is unable to reproduce the observed light-dependent phase responses. Indeed, we find that the depression of the transcriptional activator white-collar-1, previously shown to be promoted by FRQ and VVD, is a key molecular mechanism for accurately simulating light-induced phase response curves for wild-type and mutant strains of Neurospora. Our findings elucidate specific molecular pathways that can be utilized to control phase resetting of circadian rhythms.