Abstract
Our lab’s overarching goal is to characterize gene by environment etiologies of neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD). Although we know NDDs are multifactorial, relatively little is known about the specific gene by environment interactions that give rise to them. Our model organism, Drosophila melanogaster, is ideal because fruit flies are inexpensive, have a fast generation time from egg to adult, and it is estimated that approximately 60% of disease-associated genes have functional orthologs in Drosophila. Loss-of-function mutations in one of these genes that we study—Fragile X Mental Retardation 1 (FMR1/dfmr1)—are the most common monogenic cause of ASD. Bisphenols are a group of environmentally prevalent chemicals found in plastics and epoxy resins that have well-established endocrine-disrupting characteristics and may potentially influence neurodevelopment. For this project, we hypothesized that bisphenol A (BPA) exposure would disrupt the neurodevelopment of wild-type (WT) flies and would exhibit a synergistic response in combination with dfmr1. Our results indicate that BPA exposure causes midline crossing defects in the adult mushroom body—a neural structure critical for higher order sensory integration—of WT flies in a non-monotonic manner while demonstrating a neuroprotective response in dfmr1 flies. Our data also indicates that BPA exposure reduces the number of mitotically active cells in the central larval brains of WT, but not in dfmr1 flies.