BioMed CentralPage 1 of 11(page number not for citation purposes)BMC NeuroscienceOpen AccessResearch articleRegulation of prokineticin 2 expression by light and the circadian clockMichelle Y Cheng1, Eric L Bittman2, Samer Hattar3 and Qun-Yong Zhou*1Address: 1Department of Pharmacology, University of California, Irvine, CA, USA, 2Department of Biology, University of Massachusetts, Amherst, MA, USA and 3Departments of Biology and Neuroscience, Johns Hopkins University, Baltimore, MD, USAEmail: Michelle Y Cheng - mycheng@uci.edu; Eric L Bittman - elb@bio.umass.edu; Samer Hattar - shattar@jhu.edu; Qun-Yong Zhou* - qzhou@uci.edu* Corresponding author AbstractBackground: The suprachiasmatic nucleus (SCN) contains the master circadian clock thatregulates daily rhythms of many physiological and behavioural processes in mammals. Previously wehave shown that prokineticin 2 (PK2) is a clock-controlled gene that may function as a critical SCNoutput molecule responsible for circadian locomotor rhythms. As light is the principal zeitgeberthat entrains the circadian oscillator, and PK2 expression is responsive to nocturnal light pulses, wefurther investigated the effects of light on the molecular rhythm of PK2 in the SCN. In particular,we examined how PK2 responds to shifts of light/dark cycles and changes in photoperiod. We alsoinvestigated which photoreceptors are responsible for the light-induced PK2 expression in theSCN. To determine whether light requires an intact functional circadian pacemaker to regulatePK2, we examined PK2 expression in cryptochrome1,2-deficient (Cry1-/-Cry2-/-) mice that lackfunctional circadian clock under normal light/dark cycles and constant darkness.Results: Upon abrupt shifts of the light/dark cycle, PK2 expression exhibits transients in responseto phase advances but rapidly entrains to phase delays. Photoperiod studies indicate that PK2responds differentially to changes in light period. Although the phase of PK2 expression expands asthe light period increases, decreasing light period does not further condense the phase of PK2expression. Genetic knockout studies revealed that functional melanopsin and rod-conephotoreceptive systems are required for the light-inducibility of PK2. In Cry1-/-Cry2-/- mice that lacka functional circadian clock, a low amplitude PK2 rhythm is detected under light/dark conditions,but not in constant darkness. This suggests that light can directly regulate PK2 expression in theSCN.Conclusion: These data demonstrate that the molecular rhythm of PK2 in the SCN is regulatedby both the circadian clock and light. PK2 is predominantly controlled by the endogenous circadianclock, while light plays a modulatory role. The Cry1-/-Cry2-/- mice studies reveal a light-driven PK2rhythm, indicating that light can induce PK2 expression independent of the circadian oscillator. Thelight inducibility of PK2 suggests that in addition to its role in clock-driven rhythms of locomotorbehaviour, PK2 may also participate in the photic entrainment of circadian locomotor rhythms.Published: 11 March 2005BMC Neuroscience 2005, 6:17doi:10.1186/1471-2202-6-17Received: 17 November 2004Accepted: 11 March 2005This article is available from: http://www.biomedcentral.com/1471-2202/6/17© 2005 Cheng et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
