title: Distribution of TMEM100 in the mouse and human gastrointestinal tract--a novel marker of enteric nerves.
abstract: Identification of markers of enteric neurons has contributed substantially to our understanding of the development, normal physiology, and pathology of the gut. Previously identified markers of the enteric nervous system can be used to label all or most neuronal structures or for examining individual cells by labeling just the nucleus or cell body. Most of these markers are excellent but have some limitations. Transmembrane protein 100 (TMEM100) is a gene at locus 17q32 encoding a 134-amino acid protein with two hypothetical transmembrane domains. TMEM100 expression has not been reported in adult mammalian tissues but does appear in the ventral neural tube of embryonic mice and plays a role in signaling pathways associated with development of the enteric nervous system. We showed that TMEM100 messenger RNA is expressed in the gastrointestinal tract and demonstrated that TMEM100 is a membrane-associated protein. Furthermore TMEM100 immunoreactivity was restricted to enteric neurons and vascular tissue in the muscularis propria of all regions of the mouse and human gastrointestinal tract. TMEM100 immunoreactivity colocalized with labeling for the pan-neuronal marker protein gene product 9.5 (PGP9.5) but not with the glial marker S100ß or Kit, a marker of interstitial cells of Cajal. The signaling molecule, bone morphogenetic protein (BMP) 4, was also expressed in enteric neurons of the human colon and co-localized with TMEM100. TMEM100 is also expressed in neuronal cell bodies and fibers in the mouse brain and dorsal root ganglia. We conclude that TMEM100 is a novel, membrane-associated marker for enteric nerves and is as effective as PGP9.5 for identifying neuronal structures in the gastrointestinal tract. The expression of TMEM100 in the enteric nervous system may reflect a role in the development and differentiation of cells through a transforming growth factor β, BMP or related signaling pathway.
authors.affiliation: Enteric Neuroscience Program, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA.
authors.forename: S T
authors.initials: ST
authors.lastname: Eisenman
authors.forename: S J
authors.initials: SJ
authors.lastname: Gibbons
authors.forename: R D
authors.initials: RD
authors.lastname: Singh
authors.forename: C E
authors.initials: CE
authors.lastname: Bernard
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.forename: M G
authors.initials: MG
authors.lastname: Sarr
authors.forename: M L
authors.initials: ML
authors.lastname: Kendrick
authors.forename: D W
authors.initials: DW
authors.lastname: Larson
authors.forename: E J
authors.initials: EJ
authors.lastname: Dozois
authors.forename: K R
authors.initials: KR
authors.lastname: Shen
authors.forename: G
authors.initials: G
authors.lastname: Farrugia
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D002461:Cell Line, Transformed; D017615:Enteric Nervous System / Q000166:cytology / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D014162:Transfection; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C584320:TMEM100 protein, human; C556658:Tmem100 protein, mouse; C482860:UCHL1 protein, human; D019009:Proto-Oncogene Proteins c-kit; D043222:Ubiquitin Thiolesterase