Stirtz, E. | Search bioRxiv

bioRxiv2026

A Drosophila screen identifies domino as a link between chromatin regulation and synaptic organization

While heterozygous gene-disrupting variants in dosage-sensitive genes are strongly implicated in autism spectrum disorder (ASD), their effects on behavior in vivo remain poorly understood. To address this, we conducted a targeted behavioral screen in Drosophila using high-confidence ASD risk genes. This screen identified 48 lines with altered sleep, activity, or social behavior, including many genes not previously known to regulate these behaviors. The chromatin remodeler domino (dom) emerged as a compelling hit. Heterozygous mutants showed altered social spacing and male-biased changes in sleep and activity. RNA-sequencing revealed changes in gene expression and splicing associated with synaptic pathways. Consistent with these molecular changes, immunofluorescence revealed increased presynaptic activity in a brain region associated with sleep and sensory processing. Together, these findings show that partial loss of ASD risk genes is sufficient to alter behavior and identify dom as a link between transcriptional regulation, synaptic organization and behavior.

neuroscience↗

bioRxiv2025

Mutation of the white gene in Drosophila has broad phenotypic and transcriptomic effects

The white (w) gene, one of the most widely used genetic markers in Drosophila research, serves as a standard background mutation for transgene insertions and genetic manipulations1. While its primary function involves eye pigmentation, mutations in white have been associated with diverse phenotypic effects, including those related to metabolism, behavior, and stress responses2-19. However, many studies using these mutants do not account for differences in genetic background, raising concerns about the interpretation of experimental results. To ensure that the observed phenotypic differences are attributable to white itself, rather than other genetic differences due to background, we established isogenic fly strains through backcrossing that differ only by the presence or absence of the white gene. Given the likely metabolic consequences of white gene deletion and its crucial role in neurotransmitter production, we focused our phenotyping assays on behavioral, metabolic, and fitness-related outcomes and performed transcriptomic analysis on adult fly heads. Our findings reveal widespread changes in adult brain gene expression and behavioral, metabolic, and fitness traits, demonstrating that loss of white influences multiple biological processes beyond its established role in eye pigmentation. These results emphasize the necessity of genetic background control in Drosophila research and warrant caution when using white mutants as a baseline for comparative studies.

genetics↗