Circadian systems include slave oscillators and central pacemakers, and the cores of eukaryotic circadian clocks described to date are composed of transcription and translation feedback loops (TTFLs). In the model system Neurospora, normal circadian rhythmicity requires a TTFL in which a White Collar complex (WCC) activates expression of the frequency (frq) gene, and the FRQ protein feeds back to attenuate that activation. To further test the centrality of this TTFL to the circadian mechanism in Neurospora, we used low-amplitude temperature cycles to compare WT and frq-null strains under conditions in which a banding rhythm was elicited. WT cultures were entrained to these temperature cycles. Unlike those normal strains, however, frq-null mutants did not truly entrain to the same cycles. Their peaks and troughs always occurred in the cold and warm periods, respectively, strongly suggesting that the rhythm in Neurospora lacking frq function simply is driven by the temperature cycles. Previous reports suggested that a FRQ-less oscillator (FLO) could be entrained to temperature cycles, rather than being driven, and speculated that the FLO was the underlying circadian-rhythm generator. These inferences appear to derive from the use of a phase reference point affected by both the changing waveform and the phase of the oscillation. Examination of several other phase markers as well as results of additional experimental tests indicate that the FLO is, at best, a slave oscillator to the TTFL, which underlies circadian rhythm generation in Neurospora.FRQ-less oscillator ͉ frq ͉ FRQ C ircadian programs in eukaryotes are widely perceived to be the output of multiple oscillatory systems based on cell intrinsic transcription and translation feedback loops (TTFLs) (1-3). In many animals and fungi, heterodimeric PAS domaincontaining transcription factors drive expression of genes encoding proteins that block the activity of their heterodimeric activators; such negative feedback loops generally are believed to make up the cores of these circadian clocks. In addition to these autonomous biological clocks, slave oscillators also exist within the panoply of circadian systems. Early studies on entrainment in Drosophila gave rise to models in which a pacemaker drove a slave oscillator that directly regulated an overt rhythmic event (4), and noncircadian slaves have since been experimentally described (e.g., ref. 5). However, because there are few molecular descriptions of slave oscillators, their existence and properties have so far chiefly been inferred from the behavior of the circadian system when exposed to Zeitgeber period lengths outside its innate frequency.At the core of the TTFL in the circadian model system Neurospora crassa are the products of the frequency ( frq), white collar-1 (wc-1), and wc-2 genes. Similar to animal systems, Neurospora possesses a feedback loop in which a heterodimeric activator, the White Collar complex (WCC) of the PAS proteins WC-1 and WC-2, activates expression of frq and thus FRQ, which in turn ...

The metronomic predictability of the environment has elicited strong selection pressures for the evolution of endogenous circadian clocks. Circadian clocks drive molecular and behavioural rhythms that approximate the 24 h periodicity of our environment. Found almost ubiquitously among phyla, circadian clocks allow preadaptation to rhythms concomitant with the natural cycles of the Earth. Cycles in light intensity and temperature for example act as important cues that couple circadian clocks to the environment via a process called entrainment. This review summarizes our current understanding of the general and molecular principles of entrainment in the model organism Neurospora crassa, a simple eukaryote that has one of the best-studied circadian systems and light-signalling pathways.

The metronomic predictability of the environment has elicited strong selection pressures for the evolution of endogenous circadian clocks. Circadian clocks drive molecular and behavioural rhythms that approximate the 24 h periodicity of our environment. Found almost ubiquitously among phyla, circadian clocks allow preadaptation to rhythms concomitant with the natural cycles of the Earth. Cycles in light intensity and temperature for example act as important cues that couple circadian clocks to the environment via a process called entrainment. This review summarizes our current understanding of the general and molecular principles of entrainment in the model organism Neurospora crassa, a simple eukaryote that has one of the best-studied circadian systems and light-signalling pathways.

Light is one of the major signals that keep biological clocks in harmony with the outside world. Consequently, if we want to understand how circadian clocks function at the molecular level, a study of the lightinput pathways to the clock is of fundamental importance.