Molecular Systems Biology (2006) doi:10.1038/msb4100105& 2006 EMBO and Nature Publishing Group All rights reserved 1744-4292/06
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Article number: 60

NEWS AND VIEWS

Systems biology ﬂowering in the plant clock ﬁeld
Hiroki R Ueda
Center for Developmental Biology, RIKEN, Chuo-ku, Kobe, Hyogo, Japan

Molecular Systems Biology 14 November 2006; doi:10.1038/msb4100105
In the 18th Century, the Swedish botanist Karl von Linné
designed a ‘Flower-Clock’ by arranging a series of various
plant species according to the respective time their ﬂowers
open or close every day. Watching this ‘Flower-Clock’, one canthen estimate the time of the day by noting the pattern of
ﬂower opening and closing. It has been a well-known fact
since Linné’s early times that plants can open or close theirﬂowers at a precise time of the day. However, we still do not
fully understand the design principles of the molecular
network that underlies the cellular circadian clock, which
achieves to predict, often with exquisite precision, the cyclicchanges in the environment due to the rotation of earth. In two
articles currently published in Molecular Systems Biology,
Millar and co-workers (Locke et al, 2006) and Doyle andco-workers (Zeilinger et al, 2006) propose a plausible designfor the plant circadian clock.
In previous work, Millar and co-workers extended an initial‘one-loop model’ of the plant circadian clock into a ‘two-loopmodel’ (Figure 1) (Locke et al, 2005). In the simple ‘one-loopmodel’ (Figure 1, loop I), two partially redundant genes, LATEELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCKASSOCIATED 1 (CCA1), repress the expression of theiractivator, TIMING OF CAB EXPRESSION 1 (TOC1) (Alabadiet al, 2001). In this model, light activates the expression ofLHY/CCA1, according to experimental data that show a
response of LHY and CCA1 transcription to light stimulation(Wang and Tobin, 1998; Martinez-Garcia et al, 2000; Kim et al,2003). The simple ‘one-loop model’ cannot explain someexperimental data, such as the short period rhythm in lhy;cca1mutants (Alabadi et al, 2002; Locke et al, 2005). In order toexplain the residual rhythm in lhy;cca1 plants, Millar and coworkers incorporated two hypothetical components, X and Y,
to develop a ‘two-loop model’ (Figure 1, loops I and II). In thisextended model, TOC1 is proposed to activate the expressionof X, which, in turn, activates LHY/CCA1 transcription, asrequired by the time-course proﬁle of TOC1 protein (Mas et al,2003b). The second loop is formed by Y and TOC1, and isresponsible for the short-period oscillation in the lhy;cca1
mutant. Y is also proposed to be activated by light, because
TOC1 transcription has been shown to respond to light,
although there is no evidence of direct light activation of TOC1transcription (Makino et al, 2001). Although the ‘two-loop
model’ can explain many aspects of plant circadian clocks(Locke et al, 2005), it still cannot explain some experimental
data, including the residual short-period rhythm observedin the toc1 mutants (Mas et al, 2003a) and the very longperiod rhythm of double mutants for PSEUDO-RESPONSE
REGULATOR 7 (PRR7) and PRR9 (Farre et al, 2005).
& 2006 EMBO and Nature Publishing GroupIn order to explain the latter experimental results, Millar andco-workers (Locke et al, 2006) and Doyle and co-workers(Zeilinger et al, 2006) incorporated the recently proposed
feedback loop between PRR7/PRR9 and LHY/CCA1 (Farre et al,2005; Salome and McClung, 2005) and proposed a further
extension of the model into a ‘three-loop model’ (Figure 1,loops I–III). In this new model, PRR7/PRR9 are proposed to beactivated by LHY/CCA1, although PRR7/PRR9 proteinsrepress LHY/CCA1 transcription. Light activates the expression of PRR7/PRR9 in Millar’s study, or PRR9 in Doyle’smodel, as PRR9 has been shown to be acutely activated by light(Ito et al, 2003). Millar’s and Doyle’s models are very similar in
their global structure, but differ slightly in how light inductionof Yand LHY/CCA1 is modeled, and in the details of the PRR7/
PRR9-LHY/CCA1 loop mechanism. For example, Millar’s
model assumes that light induction of Y and LHY/CCA1
depends on both a continuous and a transient mechanism,
whereas Doyle and co-workers propose a more sophisticatedmechanism, whereby light induction of Y is dependent ona continuous mechanism, whereas that of LHY/CCA1 isdependent on a transient mechanism. For the purpose ofsimpliﬁcation, PRR7/PRR9 are dealt as one factor in Millar’swork, whereas PRR7 and PRR9 are more realistically treated as
two different factors in Doyle’s model. It is also noteworthy
that Millar and co-workers analyzed the rhythms of gi;lhy;cca1
triple mutant plants to further experimentally validate

Figure 1 Schematic representation of the proposed models of the plantcircadian clock. X and Y are hypothetical proteins. Yellow arrows indicate lightinput.
Molecular Systems Biology 2006 1

News and Views
HR Uedatheir proposal that GI is a strong candidate for being partof the hypothetical Y component (Locke et al, 2006), and that
Doyle’s and co-workers performed a detailed sensitivity
analysis to identify the points of strength and weakness inthe current ‘three-loop model’, thus providing a guide for
future experimental and modeling efforts (Zeilinger et al,2006).
In both cases, the ‘three-loop model’ suggests an interesting
design principle underlying the plant clock. The morning
oscillator, PRR7/PRR9-LHY/CCA1 loop (Figure 1, loop III),and the evening oscillator, TOC1-Y loop (Figure 1, loop II), arecoupled together via the LHY/CCA1-TOC1-X loop (Figure 1,loop I). These coupled morning and evening oscillators may
provide the ﬂexibility to track dawn and dusk and, thus, confer
the clock with the capability of measuring the length of the day(or intervals of multiple phases) under conditions of changing
photoperiods. In order to formally prove the proposed ‘threeloop model’, it will be necessary to uncover the identity of themissing factor X linking the morning and evening oscillators.
Only time will tell how plausible biologically signiﬁcant the‘three-loop model’ really is, but the perspective that an Xmutation will cause the morning and evening oscillators to run
with different periods within the same cell is surely an exciting
one. We can only hope that such a discovery will be reported
in the near future!

References
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Alabadi D, Yanovsky MJ, Mas P, Harmer SL, Kay SA (2002) Critical rolefor CCA1 and LHY in maintaining circadian rhythmicity inArabidopsis. Curr Biol 12: 757–761

2 Molecular Systems Biology 2006

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