Aki Murashima

Publications (4)11.13 Total impact

• Article: The role of sonic hedgehog-Gli2 pathway in the masculinization of external genitalia.

  Shinichi Miyagawa, Daisuke Matsumaru, Aki Murashima, Akiko Omori, Yoshihiko Satoh, Ryuma Haraguchi, Jun Motoyama, Taisen Iguchi, Naomi Nakagata, Chi-Chung Hui, Gen Yamada
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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. · 4.46 Impact Factor
• Article: Essential roles of androgen signaling in Wolffian duct stabilization and epididymal cell differentiation.

  Aki Murashima, Shinichi Miyagawa, Yukiko Ogino, Hisayo Nishida-Fukuda, Kimi Araki, Takahiro Matsumoto, Takehito Kaneko, Kazuya Yoshinaga, Ken-ichi Yamamura, Takeshi Kurita, Shigeaki Kato, Anne M Moon, Gen Yamada
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  ABSTRACT: The epididymis is a male accessory organ and functions for sperm maturation and storage under the control of androgen. The development of the epididymis is also androgen dependent. The Wolffian duct (WD), anlagen of the epididymis, is formed in both male and female embryos; however, it is stabilized only in male embryos by testicular androgen. Androgen drives subsequent differentiation of the WD into the epididymis. Although the essential roles of androgen in WD masculinization and epididymal function have been established, little is known about cellular events regulated precisely by androgen signaling during these processes. It is also unclear whether androgen signaling, especially in the epithelia, has further function for epididymal epithelial cell differentiation. In this study we examined the cellular death and proliferation controlled by androgen signaling via the androgen receptor (AR) in WD stabilization. Analyses using AR knockout mice revealed that androgen signaling inhibits epithelial cell death in this process. Analysis of AP2α-Cre;AR(flox/Y) mice, in which AR function is deleted in the WD epithelium, revealed that epithelial AR is not required for the WD stabilization but is required for epithelial cell differentiation in the epididymis. Specifically, loss of epithelial AR significantly reduced expression of p63 that is essential for differentiation of basal cells in the epididymal epithelium. We also interrogated the possibility of regulation of the p63 gene (Trp63) by AR in vitro and found that p63 is a likely direct target of AR regulation.
  Endocrinology 02/2011; 152(4):1640-51. · 4.46 Impact Factor
• Article: Gene transduction by sonoporation.

  Sho Ohta, Kentaro Suzuki, Yukiko Ogino, Shinichi Miyagawa, Aki Murashima, Daisuke Matsumaru, Gen Yamada
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  ABSTRACT: Gene transduction technologies are essential tools for understanding of gene functions or gene cascades underlying embryogenesis. In this review, we introduce a gene transduction method using microbubble and ultrasound (hereafter referred to as sonoporation). Sonoporation is carried out with relatively simple procedures and easily transduces genes into mesenchymal cells without significant damage to target tissues. Therefore, sonoporation is effective for gene transduction to study the molecular mechanisms of morphogenesis.
  Embryologia 05/2008; 50(6):517-20. · 2.21 Impact Factor
• Article: [FGF-mutant mice].

  Shinichi Miyagawa, Daisuke Matsumaru, Mika Kamimura, Aki Murashima, Kenichiro Mihara, Gen Yamada
  Nippon rinsho. Japanese journal of clinical medicine 11/2005; 63 Suppl 10:492-7.