Figure 1.

Scheme of four different models for the central negative feedback loop(s). Models based on different clock gene sets have been described for (A) Drosophila and other Brachycera, (B) the cricket Gryllus bimaculatus, (C) the cockroach Rhyoparobia maderae and (D) the honey bee Apis mellifera and other Hymenoptera. Different sets of clock proteins (left side of the schemes) build different combinations of dimers, which regulate the cyclic expression of clock gene mRNAs, which in turn provide the basis of clock protein production. In all four systems, the rhythms are generated by a negative feedback of some clock proteins on their transcriptional activators CLK/CYC, but there are differences in the composition of these clock proteins and their properties. In Brachycera, CRY1 acts as a blue-light receptor and can bind TIM1 (A), causing degradation of TIM1 in a light dependent manner. In contrast, the cricket relies purely on photoreception in the compound eye and CRY1 acts together with different isoforms of CRY2 (CRY2c and CRY2f) as part of a second central negative feedback loop (B). In all models, except for the Brachycera model, cyc was expressed rhythmically and Clk constitutively. Nonetheless, cyc knock-down studies showed, that Clk expression cycles in the absence of CYC, which implies that Clk expression is rhythmically regulated in crickets and rhythms are masked in the natural state (Uryu et al., 2013). It is highly likely that more than four different insect clock models for the central negative feedback loop exist, because in sand flies for example, both Clk and cyc are rhythmically expressed (Meireles-Filho et al., 2006a,b; Meireles-Filho and Kyriacou, 2013).