Analysis of the developmental cascade of the mammalian external genitalia

• Project/Area Number: 16086208
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kumamoto University
• Principal Investigator: YAMADA Gen Kumamoto University, 生命資源研究・支援センター, 教授 (80174712)
• Project Period (FY): 2004 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥93,000,000 (Direct Cost: ¥93,000,000); Fiscal Year 2008: ¥18,600,000 (Direct Cost: ¥18,600,000); Fiscal Year 2007: ¥18,600,000 (Direct Cost: ¥18,600,000); Fiscal Year 2006: ¥18,600,000 (Direct Cost: ¥18,600,000); Fiscal Year 2005: ¥18,600,000 (Direct Cost: ¥18,600,000); Fiscal Year 2004: ¥18,600,000 (Direct Cost: ¥18,600,000)
• Keywords: 生殖器 / 性分化 / 器官形成 / 細胞増殖因子 / 発生プログラム / 器管形成 / 生殖 / ノックアウトマウス / ヘッジホッグ

Research Abstract

哺乳類外生殖器形成に関わる細胞増殖因子系の機能を世界で初めて明らかにした。胎児後端において総排泄腔近傍から発生する外生殖器の組織系譜を解明し、生殖器官が協調して発生するメカニズム解明を行なった。細胞増殖因子群として重要なWnt 群の機能解析を行なった。本プロジェクトにより初めて哺乳類外生殖器の器官形成カスケードが解明され、有力国際学術雑誌に発表を行ない世界の研究をリードした。

Research Products

• [Journal Article] Embryonic hair follicle fate change by augmented β-catenin through Shh and Bmp signaling (2009)
  • Author(s): Suzuki, K., and Yamada, G
  • Journal Title: Development 136 Pages: 367-372
  • NAID: 120002468683
  • Peer Reviewed
• [Journal Article] Genetic interactions of the Androgen and Wnt/b-catenin Pathways for the Masculinization of External Genitalia (2009)
  • Author(s): Miyagawa, S.
  • Journal Title: Molecular Endocrinology (印刷中)
  • Peer Reviewed
• [Journal Article] Embryonic hair follicle fate change by augmented β-catenin through Shh and Bmp signaling (2009)
  • Author(s): Suzuki, K.
  • Journal Title: Development 136 Pages: 367-372
  • Peer Reviewed
• [Journal Article] Mouse Shh is required for prechordal plate maintenance during brain and craniofacial Morphogenesis (2009)
  • Author(s): Aoto, K.
  • Journal Title: Dev Biol 327 Pages: 106-20
  • Peer Reviewed
• [Journal Article] 皮膚バイオロジーから見えてきた増殖因子シグナルクロストークによる細胞系譜制御 ; 皮膚発生から生殖系発生メカニズムの解明に向けて (2009)
  • Author(s): 鈴木堅太郎
  • Journal Title: 細胞工学 3 Pages: 272-3
  • Peer Reviewed
• [Journal Article] Positive regulation of steroidogenic acute regulatory protein (StAR) gene expression through the interaction between Dlx and GATA-4 for testicular steroidogenesis (2008)
  • Author(s): Nishida, H., and Yamada, G.
  • Journal Title: Endocrinology 149 Pages: 2090-7
  • Peer Reviewed
• [Journal Article] Positive regulation of steroidogenic acute regulatory protein (StAR) gene expression through the interaction between Dlx and GATA-4 for testicular steroidogenesis. (2008)
  • Author(s): Nishida H
  • Journal Title: Endocrinology 149 Pages: 2090-7
  • Peer Reviewed
• [Journal Article] Abnormal urethra formation in mouse models of Split-hand/split-foot malformation type (2008)
  • Author(s): Suzuki K
  • Journal Title: Eur J Hum Genet 16 Pages: 36-44
  • Peer Reviewed
• [Journal Article] Gene expression analyses on the embryonic external genitalia : identification of regulatory genes possibly involved in masculinization processes (2008)
  • Author(s): Nishida H
  • Journal Title: Congenital Anomalies 48 Pages: 63-7
  • Peer Reviewed
• [Journal Article] Gene transduction by Sonoporation (2008)
  • Author(s): Ohta S.
  • Journal Title: Dev Growth Differ 50 Pages: 517-20
  • Peer Reviewed
• [Journal Article] Wnt5a regulates directional cell migration and cell proliferation via Ror2-mediated noncanonical pathway in mammalian palate development (2008)
  • Author(s): He, F.
  • Journal Title: Development 135 Pages: 3871-9
  • Peer Reviewed
• [Journal Article] TAK1 binding protein 1, TAB1, mediates osmotic stress-induced TAK1 activation but is dispensable for TAK1-mediated cytokine signaling (2008)
  • Author(s): Inagaki,M.
  • Journal Title: J Biol Chem 283 Pages: 33080-6
  • Peer Reviewed
• [Journal Article] Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse (2008)
  • Author(s): Ohnishi, N.
  • Journal Title: Proc Natl Acad Sci USA 105 Pages: 1003-8
  • Peer Reviewed
• [Journal Article] Generation of a conditional mutant allele for Tabl in mouse (2008)
  • Author(s): Inagaki, M.
  • Journal Title: Genesis 46 Pages: 431-9
  • Peer Reviewed
• [Journal Article] Prostate expression of endothelins and their receptors in rat growth (2008)
  • Author(s): Wada, Y.
  • Journal Title: Reprod Fertil Dev 20 Pages: 750-9
  • Peer Reviewed
• [Journal Article] EMT研究がいま面白い (2008)
  • Author(s): 山田源監修
  • Journal Title: 細胞工学 4 Pages: 314-367
  • Peer Reviewed
• [Journal Article] Positive regulation of steroidogenic acute regulatory protein (StAR) gene expression through the interaction between Dlx and GATA-4 for testicular steroidogenesis. (2008)
  • Author(s): Nishida H.
  • Journal Title: Endocrinology (In press)
  • Peer Reviewed
• [Journal Article] Gene transduction by Sonoporation. (2008)
  • Author(s): Ohta S.
  • Journal Title: Dev Growth Differ. (In press)
  • Peer Reviewed
• [Journal Article] Gene expression analyses on the embryonic external genitalia: identification of regulatory genes possibly involved in masculinization processes. Congenital Anomalies (2008)
  • Author(s): Nishida H.
  • Journal Title: Congenital Anomalies (In press)
  • Peer Reviewed
• [Journal Article] Abnormal urethra formation in mouse models of Split-hand/split-foot malformation type (2008)
  • Author(s): Suzuki K.
  • Journal Title: Eur J Hum Genet 16 Pages: 36-44
  • Peer Reviewed
• [Journal Article] Cessation of gastrulation is mediated by suppression of Epithelial-Mesenchymal Transition (EMT) at the Ventral ectodermal ridge (2007)
  • Author(s): Ohta, S., Suzuki, K., Tachibana, K., Tanaka, H. and Yamada, G.
  • Journal Title: Development 134 Pages: 4315-24
  • Peer Reviewed
• [Journal Article] Molecular analysis of coordinated bladder and urogenital organ formation by Hedgehog signaling (2007)
  • Author(s): Haraguchi, R., and Yamada, G.
  • Journal Title: Development 134 Pages: 525-533
  • NAID: 120002468518
  • Peer Reviewed
• [Journal Article] Cessation of gastrulation is mediated by suppression of Epithelial-Mesenchymal Transition (EMT) at the Ventral ectodermal ridge. (2007)
  • Author(s): Ohta S.
  • Journal Title: Development 24 Pages: 4315-24
  • Peer Reviewed
• [Journal Article] Molecular analysis of coordinated bladder and urogenital organ formation by Hedgehog signaling. (2007)
  • Author(s): Haraguchi R.
  • Journal Title: Development 134 Pages: 525-533
  • Peer Reviewed
• [Journal Article] A high-resolution anatomical ontology of the developing murinegenitourinary tract. (2007)
  • Author(s): Little, M.H.
  • Journal Title: Gene Expr Patterns 7 Pages: 680-99
  • Peer Reviewed
• [Journal Article] Regional differences in the functional and biochemical properties of endothelin receptor subtypes in the rabbit prostatic urethra. (2007)
  • Author(s): Wada Y.
  • Journal Title: BJU Int. 100 Pages: 430-7
  • Peer Reviewed
• [Journal Article] A high-resolution anatomical ontology of the developing murine genitourinary tract. (2007)
  • Author(s): Little, M.H.(他27名, 26番目)
  • Journal Title: Gene Expr Patterns (in press)
• [Journal Article] Molecular analysis of coordinated bladder and urogenital organ formation by Hedgehog signaling. (2007)
  • Author(s): Haraguchi, R.(他5名, 最後)
  • Journal Title: Development 134 Pages: 525-533
• [Journal Article] 連携して器官を発生させる : ヘッジホッグシグナルによる骨盤内外器官群の協調発生機構 (2007)
  • Author(s): 原口竜摩, 佐藤義彦, 宮川信一, 松丸大輔, 中潟直己, 山田源
  • Journal Title: 細胞工学 26(3) Pages: 296-297
• [Journal Article] Molecular genetic cascades for external genitalia formation : an emerging organogenesis program. (2006)
  • Author(s): Yamada, G., 他9名
  • Journal Title: Dev.Dyn. 235(7) Pages: 1738-1752
• [Journal Article] Cloning and expression analysis of androgen receptor gene in chicken embryogenesis. (2006)
  • Author(s): Katoh, H., Ogino, Y., Yamada, G.
  • Journal Title: FEBS Lett. 6;580(6) Pages: 1607-1615
• [Journal Article] CXorf6 is a causative gene for hypospadias. (2006)
  • Author(s): Fukami, M.(他11名, 10番目)
  • Journal Title: Nat Genet. 38(12) Pages: 1369-1371
• [Journal Article] Trace Elements in Human Tendons and Ligaments. (2006)
  • Author(s): Kumai, T.(他4名, 2番目)
  • Journal Title: Biol Trace Elem Res 114 Pages: 151-161
• [Journal Article] Intake to Vertebral Columns of Mice After Dietary Supply. (2006)
  • Author(s): Izu, A.(他6名, 6番目)
  • Journal Title: Biol Trace Elem Res. 113 Pages: 297-316
• [Journal Article] Cloning and expression analysis of androgen receptor gene in chicken embryogenesis. (2006)
  • Author(s): Katoh, H., Ogino, Y., Yamada, G.
  • Journal Title: FEBS Letters 6・580 Pages: 1607-1615
• [Journal Article] Reproductive/urogenital organ development and the molecular genetic cascades ; glamorous developmental processes of bodies. (2005)
  • Author(s): Yamada, G.(Guest Editor)
  • Journal Title: J Biochem (Tokyo). 137 Pages: 665-669
  • NAID: 10017345375
• [Journal Article] The ventral abdominal wall dysmorphogenesis of Msx1/Msx2 double-mutant mice. (2005)
  • Author(s): Ogi et al.
  • Journal Title: Anatomical Record 31 Pages: 424-430
• [Journal Article] The morphological and histological characters of the male external genitalia of the house musk shrew, Suncus murinus. (2005)
  • Author(s): Kamikawa-Miyado et al.
  • Journal Title: Zoolog Sci. 22 Pages: 463-468
• [Journal Article] TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo. (2005)
  • Author(s): Shim et al.
  • Journal Title: Genes Dev. 19 Pages: 2668-2681
• [Journal Article] Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAI-1) is Required for Branching Morphogenesis in the Chorioallantonic Placenta. (2005)
  • Author(s): Tanaka et al.
  • Journal Title: Mol. Cell. Biol. 25 Pages: 5687-5698
• [Journal Article] The cellular and molecular etiology of the cleft secondary palate in Fgf10 mutant mice. (2005)
  • Author(s): Alappat, SR. et al.
  • Journal Title: Dev Biol. 277 Pages: 102-113
• [Journal Article] Androgen dependent development of a modified anal fin, gonopodium, as a model to understand the mechanism of secondary sexual character expression in vertebrates. (2004)
  • Author(s): Ogino, Y. et al.
  • Journal Title: FEBS Lett. 575 Pages: 119-126
• [Journal Article] Regulation of external genitalia development by concerted actions of FGF ligands and FGF receptors. (2004)
  • Author(s): Satoh, Y. et al.
  • Journal Title: Anat Embryol (Berl). 208 Pages: 479-486
• [Journal Article] Bapxl regulates patterning in the middle ear : Altered regulatory role in the transition from the proximal jaw during vertebrate evolution. (2004)
  • Author(s): Tucker, A. et al.
  • Journal Title: Development 131 Pages: 1235-1245
• [Journal Article] Genetic interactions of the Androgen and Wnt/β-catenin Pathways for the Masculinization of External Genitalia
  • Author(s): Miyagawa, S., and Yamada, G.
  • Journal Title: Mol. Endocrinol. (in press)
  • Peer Reviewed
• [Journal Article] Molecular genetic cascades for external genitalia formation : an emerging organogenesis program.
  • Author(s): Yamada et al.
  • Journal Title: Dev.Dyn (in press)
• [Journal Article] The morphological and histological characters of the male external genitalia of the house musk shrew, Suncus murinus.
  • Author(s): Kamikawa-Miyado, M. et al.
  • Journal Title: Zoolog Sci. (in press)
• [Journal Article] The ventral abdominal wall dysmorphogenesis of Msx1/Msx2 double-mutant mice.
  • Author(s): Ogi, H.et al.
  • Journal Title: Anatomical Record (in press)
• [Presentation] New frontier in conditional gene knock out mouse analysis : the role of wnt/beta-catenin signals in reproductive organ and skin formation (2009)
  • Author(s): Gen Yamada
  • Organizer: The 14th Symposium of Cell and Molecular microtechnique
  • Place of Presentation: Harbin, China
  • Year and Date: 2009-01-09
• [Presentation] 細胞増殖因子カスケードと器官形成過程におけるEMT (2008)
  • Author(s): 山田源
  • Organizer: 発生工学・疾患モデル研究会第71回定例会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-21
• [Presentation] 器官形成、発生異常とWntシグナルを含む細胞増殖因子クロストーク (2008)
  • Author(s): 山田源
  • Organizer: 日本解剖学会第64回九州支部学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2008-10-25
• [Presentation] Current trend of mutant mouse analysis in the field of molecular developmental biology ; more and more mutants (2008)
  • Author(s): Gen Yamada
  • Organizer: The Asian Mouse Mutagenesis and Resource Association (AMMRA)
  • Place of Presentation: Daejeon, Korea
  • Year and Date: 2008-10-23
• [Presentation] Coordinated urogenital organ formation ; integration of growth factor cascades to regulate genital organ formation (2008)
  • Author(s): Gen Yamada
  • Organizer: International Symposium of Gonad and Brain Sex Differentiation
  • Place of Presentation: Fukuoka Japan
  • Year and Date: 2008-09-15
• [Presentation] Speakers : Ahmed Mansouri, Hongkui Deng, Jacques Drouin, Seppo Vainio, Connie Eaves, 山中伸也 (2008)
  • Author(s): Gen Yamada(オーガナイザー)
  • Organizer: The 1st Kumamoto University Global COE International Symposium on Cell Fate Regulation
  • Place of Presentation: Kumamoto, Japan
• [Presentation] (2007)
  • Author(s): Gen Yamada
  • Organizer: The 2nd Asian Mouse Mutagenesis and Resource Association (AMMRA) Meeting
  • Place of Presentation: Nanjing, China,
• [Presentation] External genitalia formation ; a glamorous developmental model system? Reproductive Tract Biology (2006)
  • Author(s): Yamada,G
  • Organizer: Gordon(ゴードン)Conference
  • Place of Presentation: New London, CT, USA.
• [Presentation] Studies relevant to mouse limbs (2006)
  • Author(s): Chairman : Gen Yamada (Speaker : Dr. Aris N Economides, Dr. Jeffrey W. Innis and Dr. Gen Yamada)
  • Organizer: 9th International Conference on Limb Development and Regeneration
  • Place of Presentation: Awaji, Japan
• [Presentation] Molecular Analysis of External Genitalia Formation : integration of growth factors and transcription factors for the regulation of Murine Genital Tubercle (GT) Development (2004)
  • Author(s): Yamada, G
  • Organizer: Mouse Molecular Genetics, CSH Meeting
  • Place of Presentation: Cold Spring Harbor, USA
• [Book] Molecular Embryology (2007)
  • Author(s): Ohta, S.(他7名, 最後)
  • Publisher: Humana Press(in press)
• [Book] DNA Deliver/Gene Transfer (2006)
  • Author(s): Ohta, S.(他5名, 最後)
  • Publisher: Cold Spring Harbor Laboratory Press
• [Book] Genetically Engineered mice Handbook (2006)
  • Author(s): Suzuki, K et al.
  • Total Pages: 314
  • Publisher: Taylor & Francis Books
• [Book] Molecular Embryology
  • Author(s): Ohta et al.
  • Publisher: Humana Press (in press)
• [Book] DNA Deliver/Gene Transfer
  • Author(s): Ohta et al.
  • Publisher: Cold Spring Harbor Laboratory Press (in press)
• [Remarks]
  • URL: http://hdl.handle.net/2298/10388
• [Remarks]
  • URL: http://hdl.handle.net/2298/10390
• [Remarks]
  • URL: http://www.imeg.kumamoto-u.ac.jp/divisions/organ_formation/