Language
English
Publication Date
1-16-2026
Journal
iScience
DOI
10.1016/j.isci.2025.114388
PMID
41561374
PMCID
PMC12814433
PubMedCentral® Posted Date
12-11-2025
PubMedCentral® Full Text Version
Post-print
Abstract
The dopaminergic system has a large role in behavior and neurological disease, and understanding dopamine level regulation in vivo is critical. To identify dopamine regulators, we utilized Drosophila melanogaster cuticle pigmentation, where dopamine is a precursor to melanin. We measured dopamine from known pigmentation mutants (e.g., tan, ebony, black) and performed an RNAi-based screen to identify additional regulators. We found 153 hits, enriched for developmental signaling pathways and mitochondria-associated proteins. From 35 prioritized candidates, 11 affected head dopamine levels. Effects on brain dopamine were mild, even knocking down the rate-limiting synthesis enzyme Tyrosine hydroxylase (TH), suggesting dopamine levels are tightly regulated in the nervous system. We pursued two hits that reduced brain dopamine levels, clueless and mask. Further examination suggests that the mask regulates the transcription of TH and affects dopamine-dependent sleep. In summary, studying genes that affect cuticle pigmentation helped to identify genes that alter dopamine metabolism and a behavioral regulator.
Keywords
model organism, neuroscience
Published Open-Access
yes
Recommended Citation
Deal, Samantha L; Bei, Danqing; Gibson, Shelley B; et al., "RNAi-Based Screen for Pigmentation in Drosophila melanogaster Reveals Regulators of Brain Dopamine and Sleep" (2026). Faculty, Staff and Students Publications. 6408.
https://digitalcommons.library.tmc.edu/baylor_docs/6408
Graphical Abstract