title: Epithelial Bmp (Bone morphogenetic protein) signaling for bulbourethral gland development: a mouse model for congenital cystic dilation.
abstract: The bulbourethral gland (BUG) is a male-specific organ, which secretes part of the semen fluid. As the BUG is located in the deep pelvic floor, its developmental process is still unclear. Bone morphogenetic protein (Bmp) signaling plays pivotal roles in various organs. However, the function of Bmp signaling for BUG development is still unclear. The present study aimed to elucidate the role of Bmp signaling in the development of the BUG. We observed the prominent nuclear accumulation of phosphorylated (p) SMAD1/5/8, the downstream molecules of Bmp signaling, during BUG epithelial development. These results suggest that Bmp signaling contributes to BUG development. Bmp receptor1a (Bmpr1a) is known as the major type 1 signal transducer in some organogeneses. To analyze the Bmp signaling function for BUG development, we examined epithelial cell-specific Bmpr1a gene conditional mutant mice utilizing the tamoxifen-inducible Cre recombinase system. We observed cystic dilation and epithelial hyperplasia of the BUG in the Bmpr1a conditional knockout mice. The mutant cystic BUG specimens also showed inflammatory lesions. These BUG abnormalities resembled some of the BUG malformations observed in human congenital syndromes. The current study suggests that Bmp signaling possesses an essential role in BUG development and homeostasis. This would be the first report showing that the mutation of the Bmpr1a gene in the BUG epithelia phenocopied some abnormalities of human congenital syndromes affecting the BUG duct.
authors.affiliation: Department of Organ Formation, Institute of Molecular Embryology and Genetics (IMEG) and Graduate School of Medical and Pharmaceutical Sciences, Kumanmoto University, Honjo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Omori
authors.forename: Masayo
authors.initials: M
authors.lastname: Harada
authors.forename: Sho
authors.initials: S
authors.lastname: Ohta
authors.forename: Mylah
authors.initials: M
authors.lastname: Villacorte
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sugimura
authors.forename: Taizou
authors.initials: T
authors.lastname: Shiraishi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakagata
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ito
authors.forename: Gen
authors.initials: G
authors.lastname: Yamada
mesh_terms: D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics* / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002030:Bulbourethral Glands / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D004108:Dilatation, Pathologic / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D004848:Epithelium / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology; D019426:Integrases / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D059952:Pelvic Floor Disorders / Q000235:genetics* / Q000473:pathology*; D015398:Signal Transduction; D051898:Smad1 Protein / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D019485:Bone Morphogenetic Proteins; D051898:Smad1 Protein; D013629:Tamoxifen; D052005:Bone Morphogenetic Protein Receptors, Type I; C045073:Cre recombinase; D019426:Integrases