Circadian photoreception in Drosophila: Functions of cryptochrome in peripheral and central clocks

In Drosophila melanogaster, disruption of night by even short light exposur es results in degradation of the clock protein TIMELESS (TIM), leading to s hifts in the fly molecular and behavioral rhythms. Several lines of evidenc e indicate that light entrainment of the brain clock involves the blue-ligh t photoreceptor cryptochrome (CRY). In cryptochrome-depleted Drosophila (cr y(b)), the entrainment of the brain clock by short light pulses is impaired but the clock is still entrainable by light-dark cycles, probably due to l ight input from the visual system. Whether cryptochrome and visual transduc tion pathways play a role in entrainment of noninnervated, directly photose nsitive peripheral clocks is not known and the subject of this study. The a uthors monitored levels of the clock protein TIM in the lateral neurons (LN s) of larval brains and in the renal Malpighian tubules (MTs) of flies muta nt for the cryptochrome gene (cry(b)) and in mutants that lack signaling fr om the visual photopigments (norpA(P41)). In cry(b) flies, light applied du ring the dark period failed to induce degradation of TIM both in MTs and in LNs, yet attenuated cycling of TIM was observed in both tissues in LD. Thi s cycling was abolished in LNs, but persisted in MTs, of norpA(P41);cry(b) double mutants. Furthermore, the activity of the tim gene in the MTs of cry (b) flies, reported by luciferase, seemed stimulated by lights-on and suppr essed by lights-off, suggesting that the absence of functional cryptochrome uncovered an additional light-sensitive pathway synchronizing the expressi on of TIM in this tissue. In constant darkness, cycling of TIM was abolishe d in MTs; however, it persisted in LNs of cry(b) flies. The authors conclud e that cryptochrome is involved in TIM-mediated entrainment of both central LN and peripheral MT clocks. Cryptochrome is also an indispensable compone nt of the endogenous clock mechanism in the examined peripheral tissue, but not in the brain. Thus, although neural and epithelial cells share the cor e clock mechanism, some clock components and light-entrainment pathways app ear to have tissue-specific roles.