Genetic and molecular analysis of circadian rhythms in Neurospora.

Over the course of the past 40 years Neurospora has become a well-known and uniquely tractable model system for the analysis of the molecular basis of eukaryotic circadian oscillatory systems. Molecular bases for the period length and sustainability of the rhythm, light, and temperature resetting of the circadian system and for gating of light input and light effects are becoming understood, and Neurospora promises to be a suitable system for examining the role of coupled feedback loops in the clock. Many of these insights have shown or foreshadow direct parallels in mammalian systems, including the mechanism of light entrainment, the involvement of PAS:PAS heterodimers as transcriptional activators in essential clock-associated feedback loops, and dual role of FRQ in the loop as an activator and a repressor; similarities extend to the primary sequence level in at least one case, that of WC-1 and BMAL1. Work on circadian output in Neurospora has identified more than a dozen regulated genes and has been at the forefront of studies aimed at understanding clock control of gene expression.