It is unclear whether neurogenesis occurs in the adult mammalian enteric nervous system (ENS). Neural crest-derived cells capable of forming multilineage colonies in culture and neurons and glia upon transplantation into chick embryos persist throughout adult life in the mammalian ENS. In this study we sought to determine the physiological function of these cells. We discovered that these cells could be identified based on CD49b expression and that they had characteristics of enteric glia including p75 GFAP S100B and SOX10 expression. To test whether new neurons or glia arise in the adult gut under physiological conditions we marked dividing progenitors with a thymidine analog in rodents under steady-state conditions or during aging pregnancy dietary changes hyperglycemia or exercise. We also tested gut injuries including inflammation irradiation benzalkonium chloride treatment partial gut stenosis and glial ablation. We readily observed neurogenesis in a neurogenic region of the central nervous system but not reproducibly in the adult ENS. Lineage tracing of glial cells with GFAP-Cre and GFAP-CreERT2 also detected little or no adult ENS neurogenesis. Neurogenesis in the adult gut is therefore very limited under the conditions we studied. In contrast ENS gliogenesis was readily observed under steady-state conditions and after injury. Adult enteric glia thus have the potential to form neurons and glia in culture but are fated to form mainly glia under physiological conditions and after the injuries we studied.
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