Microbiota controls the homeostasis of glial cells in the gut lamina propria.
Bottom Line: Here, we study how an essential subpopulation of enteric glial cells (EGCs) residing within the intestinal mucosa is integrated into the dynamic microenvironment of the alimentary tract.We find that under normal conditions colonization of the lamina propria by glial cells commences during early postnatal stages but reaches steady-state levels after weaning.Finally, we demonstrate that both the initial colonization and homeostasis of glial cells in the intestinal mucosa are regulated by the indigenous gut microbiota.
Affiliation: William Harvey Research Institute, Queen Mary University London, London EC1M 6BQ, United Kingdom; Division of Molecular Neurobiology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom. Electronic address: email@example.com.Show MeSH
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Mentions: Immunostaining of sections from adult mouse intestine for the glia-specific marker S100β displayed a dense network of EGCs extending from the MP and SMP to the lamina propria between crypts and within villi (Figure 1A). To characterize in detail the morphology of mEGCs, we combined the Sox10::Cre driver (Matsuoka et al., 2005) with the MADM-6GR and MADM-6RG alleles (Zong et al., 2005) in order to express green fluorescent protein (GFP) in subsets of peripheral glial cells (Boesmans et al., 2015). mEGCs were highly branched (Figure 1B; Movie S1) and contacted several mucosal tissues, including the epithelium, blood vessels, and neurites (Figure S1; Movies S2 and S3) (Bohórquez et al., 2014; Liu et al., 2013). The apparent interaction of mEGCs with highly regenerative and remodeling tissues of the mucosa prompted us to examine their own dynamic properties. For this, we first analyzed the developmental profile of mEGCs by immunostaining intestinal sections from Sox10::Cre;R26REYFP reporter mice at different embryonic and postnatal stages with combinations of antibodies for S100β, YFP, and the neuronal marker PGP9.5. Neuronal fibers emanating from enteric ganglia were observed in ∼50% of villi at embryonic stage (E) 16.5 and in the majority of villi at postnatal day (P) 0 (Figure S2). In contrast, the lamina propria along the villus-crypt (VC) units (Figure S2) was essentially devoid of glial cells at both E16.5 and P0 (n = 3; Figures 1C and 1F). The small fraction of glia+ VC units identified at these stages contained a single glial cell (Figure 1F). At P10 (n = 3) the percentage of glia+ VC units increased significantly and units with more than one glial cell could also be identified (Figures 1D and 1F). These parameters increased further in adult (P ≥ 60, n = 3) mice (Figures 1E and 1F). To examine the potential role of weaning on the maturation of the mEGC network, we quantified mEGCs in the ileum of mice whose age ranged from P18 to P38. At the time of gut harvesting, three animals (P18, P21, and P27) were still at the home cage with their mother (pre-weaning group), while the remaining (P27, P32, and P38) had been weaned 7 days earlier (post-weaning group). The average values of the pre-weaning and post-weaning groups were significantly different but very similar to those from P10 and adult animals, respectively (Figure 1F). Moreover, comparison of the values of the two animals that belong to different groups but have same age (P27) suggests that weaning contributes to the expansion of mEGCs observed after P10. Together, our experiments suggest that the mEGC network develops in response to signals associated with adaptation of the GI tract to the postnatal environment of the lumen and nutrition.
Affiliation: William Harvey Research Institute, Queen Mary University London, London EC1M 6BQ, United Kingdom; Division of Molecular Neurobiology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom. Electronic address: firstname.lastname@example.org.