Fig. 4: Dyrk1a-associated gut dysmotility is ameliorated by acute exposure to an SSRI or 5-HTR6 agonist.

a Schematic of a serotonergic synapse labeling the presumed location of action for the drugs tested. b Acute exposure of wildtype tadpoles to escitalopram oxalate (selective serotonin reuptake inhibitor, SSRI) alone increases the average number of fluorescent beads excreted by more than one standard deviation compared to the average DMSO treatment, blue. c Acute treatment of an SSRI (10 µM escitalopram oxalate) rescued, while a 5HTR6 agonist (10 µM WAY-181187) partially rescued the decreased fluorescent bead excretion from developmentally inhibited Dyrk1a (5 µM TG003 starting at stage NF 20) animals. d Fluorescent beads per well quantified for each treatment condition. A one-way ANOVA was performed followed by unpaired one-tailed t tests with welch’s correction. Compared to TG003 treatment (N = 6 wells, 20 tadpoles each), DMSO (N = 6 wells, 20 tadpoles each p = 0.002), TG003 + SSRI (N = 3 wells, 20 tadpoles each p = 0.0423), TG003 + WAY-181187 (N = 3 wells, 20 tadpoles each p = 0.0033). Compared to DMSO, TG003 + SSRI p = 0.4264 and TG003 + WAY-181187 p = 0.0462. All samples are independent biological replicates from the same mating pair. Data are presented as mean values +/− SEM. Source data are provided as a Source Data file. e Model of how hcASD gene large-effect variants could contribute to GI dysmotility. An hcASD genetic variant leads to perturbed ENCC migration and ultimately GI dysmotility. Created in BioRender. McCluskey, K. (2025) https://BioRender.com/n91b055.