Food consumption is one of our basic needs, yet many people experience gastrointestinal distress with almost two-thirds of Americans self-reporting symptoms. The prevalence of clinical gastrointestinal diagnoses is higher in populations with developmental disorders such as Autism, developmental delay, and Down Syndrome. These issues are often a result of gut dysmotility, which can present as constipation, diarrhea, esophageal reflux, etc, symptoms that are also significantly associated with poorer quality of life in affected individuals. Even with these high prevalence rates and impact on quality of life, the underlying biology of gastrointestinal issues is poorly understood.
The gastrointestinal tract is completely innervated and controlled by the enteric nervous system. The development of the enteric nervous system has been characterized in classic models such as chicks, mice, and zebrafish, however, little is known about how the development of the enteric nervous system may be disrupted in developmental disorders such as autism. This dissertation focuses on the question of why gastrointestinal issues are comorbid with neurodevelopmental disorders. In chapter 2, we establish Xenopus as a new model to study the development and function of the enteric nervous system. In chapter 3, we use this model and find that high-confidence autism variants are required for enteric neuron migration and gastrointestinal motility.