Concise Review: Cellular and Molecular Mechanisms of Postnatal Injury-Induced Enteric Neurogenesis

Although still controversial, there is increasing agreement that postnatal neurogenesis occurs in the enteric nervous system (ENS) in response to injury. Following acute colitis, there is significant cell death of enteric neurons and evidence suggests that subsequent neural regeneration follows. An enteric neural stem/progenitor cell population with neurogenic potential has been identified in culture; in vivo, compensatory neurogenesis is driven by enteric glia and may also include de-differentiated Schwann cells. Recent evidence suggests that changes in the enteric microenvironment due to injury-associated increases in glial cell-derived neurotrophic factor (GDNF), serotonin (5-hydroxytryptamine [HT]), products from the gut microbiome, and possibly endocannabinoids may lead to the transdifferentiation of mature enteric glia and may reprogram recruited Schwann cells. Targeting neurogenic pathways presents a promising avenue toward the development of new and innovative treatments for acquired damage to the ENS. In this review, we discuss potential sources of newly generated adult enteric neurons, the involvement of GDNF, 5-HT, endocannabinoids, and lipopolysaccharide, as well as therapeutic applications of this evolving work. Stem Cells 2019;37:1136-1143.