Fresh perspectives on how to build, maintain and repair the ENS

Enteric nervous system function is essential for survival. Studies published in 2023 have provided important novel insights into the mechanisms that regulate its development and maintenance, and demonstrate how it can be restored when these mechanisms fail.Enteric neuron differentiation trajectories branch off a fundamental gliogenic axis and mature enteric glia preserve the neurogenic properties of early enteric nervous system (ENS) progenitors5.Muscularis macrophages associated with the myenteric plexus transition from an active phagocytic profile during early postnatal stages to an ENS-protective phenotype in the adult gut8.Vagal and sacral neural crest precursors derived from human pluripotent stem cells generate distinct enteric neuron subtypes, exhibit different migratory behaviours and, when combined, can rescue a severe mouse model of Hirschsprung disease9.