title: BMPRIA is a promising marker for evaluating ganglion cells in the enteric nervous system--a pilot study.
abstract: Congenital disorders of the enteric nervous system (ENS) comprise a large group of conditions characterized by abnormalities in the number, size, or location of enteric ganglia. Their diagnosis requires careful histological evaluation of intestinal biopsies to determine the presence and morphology of these cells. Based on the recently discovered role of bone morphogenetic proteins (BMPs) in ENS development, we examined the expression of the ligands, BMP2 and BMP4, and their receptors, BMPRIA, BMPRIB, and BMPRII, during formation of the human ENS. The spatiotemporal expression pattern of these proteins suggests a role for BMP signaling in human ENS formation. We find BMPRIA, in particular, strongly and specifically expressed in all ganglion cells of the ENS at every age examined, from fetus to adult. Moreover, BMPRIA immunohistochemistry consistently allowed the identification of ganglion cells in rectal biopsies from patients with Hirschsprung disease, intestinal neuronal dysplasia, and immature ganglion cells. We propose that BMPRIA immunohistochemistry may be a promising new tool for the identification of enteric ganglion cells in the evaluation of patients with neurointestinal disorders.
authors.affiliation: Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Katherine C
authors.initials: KC
authors.lastname: Brewer
authors.forename: Olive
authors.initials: O
authors.lastname: Mwizerva
authors.forename: Allan M
authors.initials: AM
authors.lastname: Goldstein
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism*; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D004622:Embryo, Mammalian; D017615:Enteric Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D005725:Ganglia, Autonomic / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008024:Ligands; D008875:Middle Aged; D010865:Pilot Projects; D012680:Sensitivity and Specificity; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C525718:BMP2 protein, human; C525809:BMP4 protein, human; D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D008024:Ligands; D016212:Transforming Growth Factor beta; C498211:BMPR1A protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II