Enteric glia are multipotent in culture but primarily form glia in the adult rodent gut
Nancy M. Joseph, … , Gabriel Núñez, Sean J. Morrison
Nancy M. Joseph, … , Gabriel Núñez, Sean J. Morrison
Published August 25, 2011
Citation Information: J Clin Invest. 2011;121(9):3398-3411. https://doi.org/10.1172/JCI58186.
View: Text | PDF
Research Article

Enteric glia are multipotent in culture but primarily form glia in the adult rodent gut

Abstract

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.

Authors

Nancy M. Joseph, Shenghui He, Elsa Quintana, Yun-Gi Kim, Gabriel Núñez, Sean J. Morrison

×

Figure 6

Gliogenesis occurs in the adult ENS under steady-state conditions and in response to injury.

Options: View larger image (or click on image) Download as PowerPoint
Gliogenesis occurs in the adult ENS under steady-state conditions and in...
Whole mount staining of the myenteric plexus with DAPI (blue) and with antibodies against HuD (red), BrdU (green), and S100B (magenta) from normal adult mice (A) and mice that underwent focal ablation of the myenteric plexus by topical BAC treatment (B–D). BrdU was administered for 6 weeks, followed by a chase without BrdU for 6 weeks in A; and administered for 10 weeks, followed by a chase without BrdU for 3 weeks in B–D. Three mice were analyzed per treatment, with 2,000–4,000 glial cells counted per mouse. (A) 2.8% ± 0.3% of S100B+ glial cells in the myenteric plexus of healthy adult mice were BrdU+ after 6 weeks of BrdU treatment, indicating that gliogenesis does occur under steady-state conditions in the adult ENS. (B and C) Compared with uninjured mice, we observed increased frequencies (36% ± 7%) of S100B+BrdU+ glia in the myenteric plexus of BAC-treated mice, in the region bordering the injury and in healthy regions several inches upstream of the injury. (D) Almost all (90% ± 2%) S100B+ glia within the BAC-ablated region were BrdU+, suggesting a regenerative response to restore glia to the ablated region. Numbers on the bottom indicate the frequency of S100B+ myenteric plexus glia that were BrdU+ (mean ± SD). Scale bars: 50 μm.