Development of enteric neuron diversity

Neuronal diversity in the adult enteric nervous system (ENS) Developmental appearance and birthdating of enteric neuron subtypes and glial cells Developmental appearance of pan-neuronal markers and enteric neuron subtypes Time of exit from cell cycle of different neuron types Morphological development of enteric neurons Axon guidance in the developing ENS Development of connectivity Mechanisms controlling enteric neuronal differentiation and the generation of neuron diversity Transcriptional control of enteric neuronal differentiation and the generation of neuron diversity Role of glial cell line-derived neurotrophic factor (GDNF) family members in enteric neuronal differentiation and the generation of neuron diversity Role of endothelin-3/Ednrb signalling Role of other signalling pathways Neurotrophin-3 (NT-3) Bone morphogenetic proteins (BMPs) L1 Sonic hedgehog Role of electrical activity Development of enteric glia Development of neurons and neuronal subtypes in the human ENS and clinical relevance Hirschsprung's disease Is the ganglionic segment of Hirschsprung's patients 'normal'? Other paediatric motility disorders Defects in the development of subtypes of enteric neurons Defects in the number of enteric neurons Conclusions The mature enteric nervous system (ENS) is composed of many different neuron subtypes and enteric glia, which all arise from the neural crest. How this diversity is generated from neural crest-derived cells is a central question in neurogastroenterology, as defects in these processes are likely to underlie some paediatric motility disorders. Here we review the developmental appearance (the earliest age at which expression of specific markers can be localized) and birthdates (the age at which precursors exit the cell cycle) of different enteric neuron subtypes, and their projections to some targets. We then focus on what is known about the mechanisms underlying the generation of enteric neuron diversity and axon pathfinding. Finally, we review the development of the ENS in humans and the etiologies of a number of paediatric motility disorders.