Enteric Nervous System: lessons from neurogenesis for reverse engineering and disease modelling and treatment

Normal activity and functional integration of the enteric nervous system (ENS) into the gut tissue circuitry and the luminal ecosystem are essential for digestive physiology and human health. A range of debilitating gastrointestinal disorders are linked to ENS dysfunction, caused either by developmental deficits, such as congenital megacolon (Hirschsprung's disease-HSCR) or a host of acquired intestinal neuropathies with unclear molecular or cellular pathogenesis. Recent advances in cell engineering underscore the potential use of cell replacement technologies for the treatment of ENS disorders. This review will highlight strategies used to derive ENS lineages from various tissue sources intended for cell therapy and disease modelling. We will also describe how a developmental atlas of the mammalian ENS re-constructed from single cell genomics data is an essential reference for shaping future therapeutic approaches in regenerative enteric neuroscience and neuro-gastroenterology.