The Enteric Nervous System, which is the largest subdivision of the peripheral nervous system, regulates key gastrointestinal and systemic functions of digestion, metabolism, immunity, and maintenance of intestinal microbiota. Using various lineage tracing and fate-mapping transgenic models, we study the development of the ENS during post-natal life, and in adulthood, and study how these developmental processes contribute to aging. Our work has discovered a previously unknown lineage of enteric neurons that is derived from the mesoderm. We aim to interrogate the role of genetics, sex, intestinal microbiota, and other environmental factors on post-natal development and aging of the ENS. Finally, using human specimens, we aim to understand how various diseases of inflammatory, rheumatological, and metabolic origins impact the ENS to cause disease.