Abstract
Autism spectrum disorder (ASD) refers to a collection of neurodevelopmental disorders that affect an estimated 1-2% of the population worldwide. Despite being classically diagnosed and defined by impairments in socialization and communication, many forms of ASD are comorbid with physiological disruptions. Gastrointestinal (GI) comorbidities are highly represented in ASD, especially among the population of patients affected by SYNGAP1-related intellectual disability and Phelan-McDermid Syndrome (PMDS). Following previous studies in CRISPR-generated stable mutant lines of both conditions that show GI dysmotility, we sought to test the various mechanisms controlled by the brain-gut-microbe axis that could contribute to the aberrant phenotypes. We found sensory deficits in syngap1+/- enteroendocrine cells (EECs) in response to glucose, as well as reduced numbers of enteric neurons in syngap1-/- mutants. We established a method for gut explant culture to assay motility absent CNS input. Finally, we did not find evidence of microbial influence on or by the shank3 mutant phenotype but determined that further understanding of the microbiotic composition is warranted. These results further our understanding of GI dysmotility in ASD-model zebrafish and could point to potential clinical targets.