The Neurospora circadian clock: simple or complex?

Abstract

The fungus Neurospora crassa is being used by a number of research groups as a model organism to investigate circadian (daily) rhythmicity. In this review we concentrate on recent work relating to the complexity of the circadian system in this organism. We discuss: the advantages of Neurospora as a model system for clock studies; the frequency (frq), white collar-1 and white collar-2 genes and their roles in rhythmicity; the phenomenon of rhythmicity in null frq mutants and its implications for clock mechanisms; the study of output pathways using clock-controlled genes; other rhythms in fungi; mathematical modelling of the Neurospora circadian system; and the application of new technologies to the study of Neurospora rhythmicity. We conclude that there may be many gene products involved in the clock mechanism, there may be multiple interacting oscillators comprising the clock mechanism, there may be feedback from output pathways onto the oscillator(s) and from the oscillator(s) onto input pathways, and there may be several independent clocks coexisting in one organism. Thus even a relatively simple lower eukaryote can be used to address questions about a complex, networked circadian system.

Circadian rhythms in Neurospora crassa: Dynamics of the clock component frequency visualized using a fluorescent reporter

“…The fungus Neurospora crassa has been used as a model organism to investigate the components of the circadian clock that regulate molecular, physiological and behavioral activities (Dunlap, 2006). Several properties of Neurospora , such as a straightforward handling in the laboratory, an easily-observable macroscopic rhythm (banding pattern) and the availability of the complete genome sequence, make this organism an ideal one for clock research (Bell-Pedersen et al, 2001a). To improve the understanding of how the clock operates in this organism we have created tools that have already proven useful for monitoring the dynamics of the frq gene under physiological conditions.…”

“…Moreover, since periods can be measured for many days, a large number of cultures can be simultaneously monitored and manipulated. The Neurospora clock system has all of the properties of the circadian rhythm definition listed above and is one of the handful of organisms where a reasonable amount of molecular understanding is known (Bell-Pedersen et al, 2001a,b; Loros and Dunlap, 2001; Dunlap, 2006). All of the formal aspects of the Neurospora clock have been worked out from cultures growing on the surface of an agar medium, either in race tubes or plates, and most of the details of the molecular biology of the Neurospora clock system have been obtained from a mycelial disk system in a shaking liquid culture (Nakashima, 1981).…”

Natural Variation of the Circadian Clock in Neurospora

“…Although Neurospora is a simple eukaryotic organism in comparison to higher eukaryotes, the molecular structure of the Neurospora circadian clock shows significant complexity, thus providing an opportunity to dissect network motifs for more complex eukaryotic circadian systems (Bell-Pedersen, Crosthwaite, Lakin-Thomas, Merrow, & Okland, 2001). This molecular structure is composed of the negative components FREQUENCY (FRQ) and VIVID (VVD), and the positive components WHITE COLLAR-1 (WC-1), and WHITE COLLAR-2 (WC-2).…”

“…Based on these studies, a two-oscillator model has been proposed; the core circadian oscillator responds to light and FLO responds to non-photic signals such as temperature. These two oscillators may or may not be coupled to generate developmental rhythms (Bell-Pedersen et al, 2001). In addition to a Choline-Deficient Oscillator, CDO (Lakin-Thomas, 1998; Lakin-Thomas & Brody, 2000), a Farnesol or Geraniol based Oscillator, FGO (Granshaw, Tsukamoto, & Brody, 2003), and a Cryptochrome-dependent Oscillator, CRO (Nsa et al, 2015) have been identified in N. crassa .…”

“…For these reasons, Neurospora can serve as a potential model to elucidate fundamental questions of quantitative genetics for complex behaviors including circadian clocks. As our understanding of the molecular structure of circadian clocks advances, it becomes apparent that the circadian clock is more tightly linked with other cellular machinery than we imagined (Bell-Pedersen et al, 2001). Based on this, one cannot dissociate the circadian clock from basic cellular metabolism.…”