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Publications (2)4.72 Total impact

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    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.
    Congenital Anomalies 09/2011; 51(3):102-9.
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    ABSTRACT: During embryogenesis, sexually dimorphic organogenesis is achieved by hormones produced in the gonad. The external genitalia develop from a single primordium, the genital tubercle, and their masculinization processes depend on the androgen signaling. In addition to such hormonal signaling, the involvement of nongonadal and locally produced masculinization factors has been unclear. To elucidate the mechanisms of the sexually dimorphic development of the external genitalia, series of conditional mutant mouse analyses were performed using several mutant alleles, particularly focusing on the role of hedgehog signaling pathway in this manuscript. We demonstrate that hedgehog pathway is indispensable for the establishment of male external genitalia characteristics. Sonic hedgehog is expressed in the urethral plate epithelium, and its signal is mediated through glioblastoma 2 (Gli2) in the mesenchyme. The expression level of the sexually dimorphic genes is decreased in the glioblastoma 2 mutant embryos, suggesting that hedgehog signal is likely to facilitate the masculinization processes by affecting the androgen responsiveness. In addition, a conditional mutation of Sonic hedgehog at the sexual differentiation stage leads to abnormal male external genitalia development. The current study identified hedgehog signaling pathway as a key factor not only for initial development but also for sexually dimorphic development of the external genitalia in coordination with androgen signaling.
    Endocrinology 07/2011; 152(7):2894-903. · 4.72 Impact Factor