Secreted frizzled-related proteins (Sfrps) are antagonists of WNT signalling implicated in a variety of biological processes. However, there are no reports of a direct role for Sfrps in embryonic organogenesis in mammals. Using in vivo loss-of-function studies we report here for the first time a redundant role for Sfrp1 and Sfrp2 in embryonic sexual development of the mouse. At 16.5 dpc, male embryos lacking both genes exhibit multiple defects in gonad morphology, reproductive tract maturation and gonad positioning. Abnormal positioning of the testis appears to be due to failed gubernaculum development and an unusually close association between the cranial end of the reproductive tract and the kidney. The testes of double homozygotes are smaller than controls, contain fewer cords from the earliest stages, but still express Insl3, which encodes the hormone required for gubernacular masculinisation. Lgr8, which encodes the Insl3 receptor, is also expressed in the mutant gubernaculum, suggesting that Sfrpl/Sfrp2 signalling is not required for expression of the ligand or receptor that controls transabdominal testicular descent. Similarities between the abnormalities of embryonic sexual development in Sfrp1(-/-) Sfrp2(-/-) embryos with those exhibited by the Looptail and Wnt5a mutants suggest that disrupted non-canonical Wnt signalling may cause these defects. (c) 2008 Elsevier Inc. All rights reserved.
机构:
RIKEN Kobe, Ctr Dev Biol, Chouou Ku, Kobe, Hyogo 6500047, Japan
Nara Inst Sci & Technol, Grad Sch Biol Sci, Nara, JapanRIKEN Kobe, Ctr Dev Biol, Chouou Ku, Kobe, Hyogo 6500047, Japan
Satoh, Wataru
Matsuyama, Makoto
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RIKEN Kobe, Ctr Dev Biol, Chouou Ku, Kobe, Hyogo 6500047, JapanRIKEN Kobe, Ctr Dev Biol, Chouou Ku, Kobe, Hyogo 6500047, Japan
Matsuyama, Makoto
Takemura, Hiromasa
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RIKEN Kobe, Ctr Dev Biol, Chouou Ku, Kobe, Hyogo 6500047, Japan
Nara Inst Sci & Technol, Grad Sch Biol Sci, Nara, JapanRIKEN Kobe, Ctr Dev Biol, Chouou Ku, Kobe, Hyogo 6500047, Japan
Takemura, Hiromasa
Aizawa, Shinichi
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RIKEN Kobe, Ctr Dev Biol, Chouou Ku, Kobe, Hyogo 6500047, JapanRIKEN Kobe, Ctr Dev Biol, Chouou Ku, Kobe, Hyogo 6500047, Japan
Aizawa, Shinichi
Shimono, Akihiko
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RIKEN Kobe, Ctr Dev Biol, Chouou Ku, Kobe, Hyogo 6500047, JapanRIKEN Kobe, Ctr Dev Biol, Chouou Ku, Kobe, Hyogo 6500047, Japan
机构:
Natl Def Med Ctr, Grad Inst Med Sci, Taipei 114, Taiwan
Army Forces Tao Yuan Gen Hosp, Dept Obstet & Gynecol, Tao Yuan, TaiwanNatl Def Med Ctr, Dept Microbiol & Immunol, Taipei 114, Taiwan
Chung, Ming-Tzeung
Lai, Hung-Cheng
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Natl Def Med Ctr, Dept Obstet & Gynecol, Tri Serv Gen Hosp, Taipei 114, Taiwan
Natl Def Med Ctr, Lab Epigenet, Taipei 114, TaiwanNatl Def Med Ctr, Dept Microbiol & Immunol, Taipei 114, Taiwan
Lai, Hung-Cheng
Sytwu, Huey-Kang
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Natl Def Med Ctr, Grad Inst Med Sci, Taipei 114, TaiwanNatl Def Med Ctr, Dept Microbiol & Immunol, Taipei 114, Taiwan
Sytwu, Huey-Kang
Yan, Ming-De
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Natl Hlth Res Inst, Inst Canc Res, Zhunan, Miaoli County, TaiwanNatl Def Med Ctr, Dept Microbiol & Immunol, Taipei 114, Taiwan
Yan, Ming-De
Shih, Yu-Lueng
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Natl Def Med Ctr, Dept Internal Med, Div Gastroenterol, Tri Serv Gen Hosp, Taipei 114, Taiwan
Natl Def Med Ctr, Lab Epigenet, Taipei 114, TaiwanNatl Def Med Ctr, Dept Microbiol & Immunol, Taipei 114, Taiwan
Shih, Yu-Lueng
Chang, Cheng-Chang
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Natl Def Med Ctr, Dept Obstet & Gynecol, Tri Serv Gen Hosp, Taipei 114, TaiwanNatl Def Med Ctr, Dept Microbiol & Immunol, Taipei 114, Taiwan
Chang, Cheng-Chang
Yu, Mu-Hsien
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Natl Def Med Ctr, Dept Obstet & Gynecol, Tri Serv Gen Hosp, Taipei 114, TaiwanNatl Def Med Ctr, Dept Microbiol & Immunol, Taipei 114, Taiwan
Yu, Mu-Hsien
Liu, Hang-Seng
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Army Forces Tao Yuan Gen Hosp, Dept Obstet & Gynecol, Tao Yuan, TaiwanNatl Def Med Ctr, Dept Microbiol & Immunol, Taipei 114, Taiwan
Liu, Hang-Seng
Chu, Da-Wei
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Army Forces Tao Yuan Gen Hosp, Dept Obstet & Gynecol, Tao Yuan, TaiwanNatl Def Med Ctr, Dept Microbiol & Immunol, Taipei 114, Taiwan
机构:
Univ N Texas, Hlth Sci Ctr, N Texas Eye Res Inst, Dept Cell Biol & Anat, Ft Worth, TX 76107 USAUniv N Texas, Hlth Sci Ctr, N Texas Eye Res Inst, Dept Cell Biol & Anat, Ft Worth, TX 76107 USA
Mao, Weiming
Wordinger, Robert J.
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Univ N Texas, Hlth Sci Ctr, N Texas Eye Res Inst, Dept Cell Biol & Anat, Ft Worth, TX 76107 USAUniv N Texas, Hlth Sci Ctr, N Texas Eye Res Inst, Dept Cell Biol & Anat, Ft Worth, TX 76107 USA
Wordinger, Robert J.
Clark, Abbot F.
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Univ N Texas, Hlth Sci Ctr, N Texas Eye Res Inst, Dept Cell Biol & Anat, Ft Worth, TX 76107 USAUniv N Texas, Hlth Sci Ctr, N Texas Eye Res Inst, Dept Cell Biol & Anat, Ft Worth, TX 76107 USA