Reviewer #2 (Public review): Non-visual light modulates behavioral memory and gene expression in C. elegans

Visible light influences a range of physiological processes, yet how animals respond to it independently of the visual system remains largely unknown. Here, we uncover a previously undescribed light-induced transcriptional pathway that modulates behavioral plasticity in C. elegans, a roundworm without eyes. We demonstrate that ambient visible light or controlled-intensity visible-spectrum LED activates an effector gene cyp-14A5 in non-neuronal tissues through the bZIP transcription factors ZIP-2 and CEBP-2. Light induction of cyp-14A5 is more prominent at shorter wavelengths but is independent of the known blue light receptors LITE-1 and GUR-3 in C. elegans. This bZIP-dependent genetic pathway in non-neuronal tissues enhances behavioral adaptability and olfactory memory, suggesting a body-brain communication axis. Furthermore, we use the light-responsive cyp-14A5 promoter to drive ectopic gene expression, causing synthetic light-induced sleep and rapid aging phenotypes in C. elegans. These findings advance our understanding of light-responsive mechanisms outside the visual system and offer a new genetic tool for visible light-inducible gene expression in non-neuronal tissues.