title: Heterogeneity and phenotypic plasticity of glial cells in the mammalian enteric nervous system.
abstract: Enteric glial cells are vital for the autonomic control of gastrointestinal homeostasis by the enteric nervous system. Several different functions have been assigned to enteric glial cells but whether these are performed by specialized subtypes with a distinctive phenotype and function remains elusive. We used Mosaic Analysis with Double Markers and inducible lineage tracing to characterize the morphology and dynamic molecular marker expression of enteric GLIA in the myenteric plexus. Functional analysis in individually identified enteric glia was performed by Ca(2+) imaging. Our experiments have identified four morphologically distinct subpopulations of enteric glia in the gastrointestinal tract of adult mice. Marker expression analysis showed that the majority of glia in the myenteric plexus co-express glial fibrillary acidic protein (GFAP), S100β, and Sox10. However, a considerable fraction (up to 80%) of glia outside the myenteric ganglia, did not label for these markers. Lineage tracing experiments suggest that these alternative combinations of markers reflect dynamic gene regulation rather than lineage restrictions. At the functional level, the three myenteric glia subtypes can be distinguished by their differential response to adenosine triphosphate. Together, our studies reveal extensive heterogeneity and phenotypic plasticity of enteric glial cells and set a framework for further investigations aimed at deciphering their role in digestive function and disease.
authors.affiliation: Laboratory for Enteric NeuroScience (LENS), TARGID, Department of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium.
authors.forename: Werend
authors.initials: W
authors.lastname: Boesmans
authors.forename: Reena
authors.initials: R
authors.lastname: Lasrado
authors.forename: Pieter
authors.initials: P
authors.lastname: Vanden Berghe
authors.forename: Vassilis
authors.initials: V
authors.lastname: Pachnis
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D021621:Imaging, Three-Dimensional; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009197:Myenteric Plexus / Q000166:cytology*; D009457:Neuroglia / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008164:Luminescent Proteins; C484412:Mlf1 protein, mouse; D011506:Proteins; D064568:S100 Calcium Binding Protein beta Subunit; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse; D014404:Tubulin; C462941:beta3 tubulin, mouse; D000241:Adenosine; D002118:Calcium
keywords: Ca2+ imaging; enteric glia; enteric nervous system; neural crest