Novel Features of Cryptochrome-Mediated Photoreception in the Brain Circadian Clock ofDrosophila

Abstract

In Drosophila, light affects circadian behavioral rhythms via at least two distinct mechanisms. One of them relies on the visual phototransduction cascade. The other involves a presumptive photopigment, cryptochrome (cry), expressed in lateral brain neurons that control behavioral rhythms. We show here that cry is expressed in most, if not all, larval and adult neuronal groups expressing the PERIOD (PER) protein, with the notable exception of larval dorsal neurons (DN2s) in which PER cycles in antiphase to all other known cells. Forcing cry expression in the larval DN2s gave them a normal phase of PER cycling, indicating that their unique antiphase rhythm is related to their lack of cry expression. We were able to directly monitor CRY protein in Drosophila brains in situ. It appeared highly unstable in the light, whereas in the dark, it accumulated in both the nucleus and the cytoplasm, including some neuritic projections. We also show that dorsal PER-expressing brain neurons, the adult DN1s, are the only brain neurons to coexpress the CRY protein and the photoreceptor differentiation factor GLASS. Studies of various visual system mutants and their combination with the cry b mutation indicated that the adult DN1s contribute significantly to the light sensitivity of the clock controlling activity rhythms, and that this contribution depends on CRY. Moreover, all CRY-independent light inputs into this central behavioral clock were found to require the visual system. Finally, we show that the photoreceptive DN1 neurons do not behave as autonomous oscillators, because their PER oscillations in constant darkness rapidly damp out in the absence of pigment-dispersing-factor signaling from the ventral lateral neurons.

Light-arousal and circadian photoreception circuits intersect at the large PDF cells of the Drosophila brain

“…R6Gal4 labels s-LNvs and other nonclock neurons (24). cry39Gal4 or cry13Gal4 both label l-LNvs, s-LNvs, the 5th LNvs, LNds, and some of the DN1s (12,16). cry39Gal4 also labels some of the DN3s.…”

“…The 10 l-LNvs (5 on each side of the brain) are among the first circadian neurons identified in Drosophila (14), and there are some indications that they may function as coincident detectors for light (9,12,(15)(16)(17). However, they have never been assigned a circadian or behavioral function, because there are no tools available to selectively address their function.…”

Rhythm Defects Caused by Newly Engineered Null Mutations in Drosophila's cryptochrome Gene

“…The effects of the cry b mutation on such molecular rhythmicity implied that the normal gene is expressed in the periphery, but cry 1 was found also to make its products in the central nervous system (Emery et al 2000b;Klarsfeld et al 2004). In one test of cry b 's effects on whole-animal rhythm-related phenotypes, mutant individuals resynchronized their behavior in a largely normal manner to shifted light:dark (LD) cycles; ''L'' in the postshift regime was dim blue light (Stanewsky et al 1998).…”

A metal left spinning

“…The data almost defy imagination -on the order of a million cells in every cubic centimetre of sediment buried half a kilometre below the sea floor, or more than 50% of all microbial cells on Earth 12 10,11,13 , and a hung jury has been declared 14 over the question of the predominance of Bacteria or Archaea. But why the protracted debate?…”