title: Conditional deletion of beta-catenin in the mesenchyme of the developing mouse uterus results in a switch to adipogenesis in the myometrium.
abstract: Precise cell fate decisions during differentiation of uterine tissues from the embryonic Müllerian duct are critical for normal fertility. Wnt-7a, a member of the Wnt family of secreted signaling molecules that can signal through a canonical beta-catenin pathway, is necessary for the correct differentiation of both anterior/posterior and radial axes of the uterus. In order to investigate the role of beta-catenin directly in mouse uterine development, we have generated mice that are deficient in beta-catenin expression in the embryonic Müllerian duct. We have found that conditional deletion of beta-catenin in the Müllerian duct mesenchyme before postnatal differentiation of the uterine layers results in a phenotype that is distinct from the phenotype observed by deletion of Wnt-7a. Shortly after birth, the uteri of the conditional mutants appear smaller and less organized. The uteri of adult conditional beta-catenin mutants are grossly deficient in smooth muscle of the myometrium, which has been replaced by adipose, a phenotype resembling human lipoleiomyoma. We also show that the adipocytes in the uteri of mice conditionally deleted for beta-catenin are derived from Müllerian inhibiting substance type II receptor-expressing cells suggesting that they share a common origin with the uterine smooth muscle cells. These results describe the first molecular evidence linking disruption of beta-catenin expression in mesenchymal cells with a switch from myogenesis to adipogenesis in vivo.
authors.affiliation: Pediatric Surgical Research Laboratories/CPZN6202, Massachusetts General Hospital and Harvard Medical School, 185 Cambridge St., Boston, MA 02114, USA.
authors.forename: Nelson A
authors.initials: NA
authors.lastname: Arango
authors.forename: Paul P
authors.initials: PP
authors.lastname: Szotek
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Manganaro
authors.forename: Esther
authors.initials: E
authors.lastname: Oliva
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Donahoe
authors.forename: Jose
authors.initials: J
authors.lastname: Teixeira
mesh_terms: D017667:Adipocytes / Q000502:physiology; D050156:Adipogenesis / Q000235:genetics*; D000273:Adipose Tissue / Q000502:physiology; D000818:Animals; D005260:Female; D017353:Gene Deletion; D019426:Integrases / Q000096:biosynthesis / Q000235:genetics; D008648:Mesoderm / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000378:metabolism; D009215:Myometrium / Q000196:embryology* / Q000254:growth & development; D014599:Uterus / Q000196:embryology* / Q000254:growth & development; D051176:beta Catenin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
chemical_list: D051176:beta Catenin; C045073:Cre recombinase; D019426:Integrases