title: Sfrp1 and Sfrp2 are required for normal male sexual development in mice.
abstract: 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 Sfrp1/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.
authors.affiliation: Mammalian Genetics Unit, MRC Harwell, Harwell Science and Innovation Campus, Oxfordshire, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Warr
authors.forename: Pam
authors.initials: P
authors.lastname: Siggers
authors.forename: Debora
authors.initials: D
authors.lastname: Bogani
authors.forename: Rachel
authors.initials: R
authors.lastname: Brixey
authors.forename: Laura
authors.initials: L
authors.lastname: Pastorelli
authors.forename: Laura
authors.initials: L
authors.lastname: Yates
authors.forename: Charlotte H
authors.initials: CH
authors.lastname: Dean
authors.forename: Sara
authors.initials: S
authors.lastname: Wells
authors.forename: Wataru
authors.initials: W
authors.lastname: Satoh
authors.forename: Akihiko
authors.initials: A
authors.lastname: Shimono
authors.forename: Andy
authors.initials: A
authors.lastname: Greenfield
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000033:anatomy & histology* / Q000502:physiology*; D005260:Female; D005837:Genitalia, Male / Q000002:abnormalities / Q000033:anatomy & histology* / Q000196:embryology* / Q000254:growth & development; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D011247:Pregnancy; D013739:Testosterone / Q000378:metabolism; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D013739:Testosterone; C485539:Sfrp1 protein, mouse; D000094742:Secreted Frizzled-Related Proteins; C491628:Sfrp2 protein, mouse