"Remote and partial clocks expand the circadian neuronal network, driving widespread molecular rhythmicity in Drosophila"

Abstract

Circadian clocks orchestrate daily physiology and behavioral rhythms, yet the extent to which cells lacking canonical clock components exhibit robust temporal regulation remains unclear. Here we addressed this question using a two-step strategy. First, we systematically mapped core clock gene expression at single-cell resolution across the Drosophila brain and body. Second, leveraging these data and performing targeted experiments, we uncovered cells that lack most or all canonical clock components yet display strong mRNA rhythms. We found that lamina wide-field neurons show high-amplitude tim mRNA cycling even in constant darkness conditions (DD) despite minimal expression of other clock genes, suggesting a partial or noncanonical oscillator. In addition, C2 and C3 optic lobe neurons, which do not express core clock components, exhibit hundreds of circadian and daily cycling transcripts. Notably, circadian rhythms in C3 neurons coincide with oscillations of activity-regulated genes (ARGs), whereas C2 neurons cycle independently of ARGs, indicating distinct non-cell-autonomous mechanisms. These findings reveal a spectrum of circadian regulation, from autonomous to remote, input-driven rhythms and expand the circadian landscape to include strategies for generating and distributing temporal information across neuronal and non-neuronal cell types.