title: Bone morphogenetic protein expression patterns in human esophageal atresia with tracheoesophageal fistula.
abstract: The organogenesis of esophageal atresia with tracheoesophageal fistula (EA/TEF) remains unknown. The fistula tract appears to develop from a non-branching trifurcation of the embryonic lung bud. The non-branching growth of the fistula differs from the other lung buds and suggests a deficiency in bone morphogenetic protein (BMP) signaling, since BMPs are critical to proper lung development and branching. With IRB approval, portions of newborn human proximal esophageal pouch and distal fistula samples were recovered at the time of surgical repair of EA/TEF. The tissues were processed for immunohistochemistry. Commercially available fetal tissues were used as controls. In control tissues, BMP ligands (BMP 2, 4, and 7) were all present in the esophagus but absent in the trachea. BMPRIA was absent in both tissues. BMPRIB was detected in trachea but not in esophagus and BMPRII was detected in esophagus but not in trachea. In the EA/TEF specimens, all BMP ligands were present in the proximal esophageal pouch but absent in the fistula tract. BMPRIA and BMPRIB were not detected in either tissue. However, BMPRII was found in both fistula tract and proximal pouch. The submucosa of the fistula appears to maintain a mixed (identical neither to lung, esophagus, or trachea) BMP signaling pattern, providing one mechanism which could potentially explain the esophageal dismotility and lack of lung branching seen in the fistula/distal esophagus.
authors.affiliation: Laboratory for Surgical Organogenesis, Department of Surgery, Children's Mercy Hospital, 2401 Gillham Road, Kansas City, MO, 64108, USA.
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Crowley
authors.forename: Sheilendra S
authors.initials: SS
authors.lastname: Mehta
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Hembree
authors.forename: Barry L
authors.initials: BL
authors.lastname: Preuett
authors.forename: Krishna L
authors.initials: KL
authors.lastname: Prasadan
authors.forename: Susan W
authors.initials: SW
authors.lastname: Sharp
authors.forename: Hooi
authors.initials: H
authors.lastname: Yew
authors.forename: Christopher R
authors.initials: CR
authors.lastname: McFall
authors.forename: Christina L
authors.initials: CL
authors.lastname: Benjes
authors.forename: Sidhartha S
authors.initials: SS
authors.lastname: Tulachan
authors.forename: George K
authors.initials: GK
authors.lastname: Gittes
authors.forename: Charles L
authors.initials: CL
authors.lastname: Snyder
mesh_terms: D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism*; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D004933:Esophageal Atresia / Q000196:embryology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D008024:Ligands; D015398:Signal Transduction; D014138:Tracheoesophageal Fistula / Q000196:embryology* / Q000473:pathology
chemical_list: D019485:Bone Morphogenetic Proteins; D008024:Ligands; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II