Sfrp1 and Sfrp2 are required for normal male sexual development in mice

被引:72
|
作者
Warr, Nick [1 ]
Siggers, Pam [1 ]
Bogani, Debora [1 ]
Brixey, Rachel [1 ]
Pastorelli, Laura [1 ]
Yates, Laura [1 ]
Dean, Charlotte H. [1 ]
Wells, Sara [2 ]
Satoh, Wataru [3 ]
Shimono, Akihiko [3 ]
Greenfield, Andy [1 ]
机构
[1] MRC Harwell, Mammalian Genet Unit, Didcot OX11 0RD, Oxon, England
[2] MRC Harwell, Mary Lyon Ctr, Didcot OX11 0RD, Oxon, England
[3] RIKEN Kobe, Ctr Dev Biol, Chuo Ku, Kobe, Hyogo 6500047, Japan
基金
英国医学研究理事会;
关键词
Secreted frizzled-related protein; Sfrp1; Sfrp2; Mouse sexual development; Gubernaculum; Testis descent; Gonad; Reproductive tract; Wnt signalling; FRIZZLED-RELATED PROTEINS; REPRODUCTIVE-TRACT DEVELOPMENT; DIMORPHIC EXPRESSION; TESTICULAR DESCENT; SIGNALING PATHWAY; GONAD DEVELOPMENT; BETA-CATENIN; SPEMANN ORGANIZER; GENE-EXPRESSION; CELL-MIGRATION;
D O I
10.1016/j.ydbio.2008.11.023
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:273 / 284
页数:12
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