Essential roles of mesenchyme-derived beta-catenin in mouse Müllerian duct morphogenesis.
Members of the Wnt family of genes such as Wnt4, Wnt5a, and Wnt7a have been implicated in the formation and morphogenesis of the Müllerian duct into various parts of the female reproductive tract. These WNT ligands elicit their action via either the canonical WNT/beta-catenin or the non-canonical WNT/calcium pathway and could possibly function redundantly in Müllerian duct differentiation. By using the Müllerian duct-specific anti-Müllerian hormone receptor 2 cre (Amhr2-cre) mouse line, we established a conditional knockout model that removed beta-catenin specifically in the mesenchyme of the Müllerian duct. At birth, loss of beta-catenin in the Müllerian duct mesenchyme disrupted the normal coiling of the oviduct in the knockout embryo, resembling the phenotype of the Wnt7a knockout. The overall development of the female reproductive tract was stunted at birth with a decrease in proliferation in the mesenchyme and epithelium. We also discovered that Wnt5a and Wnt7a expression remained normal, excluding the possibility that the phenotypes resulted from a loss of these WNT ligands. We examined the expression of Frizzled (Fzd), the receptors for WNT, and found that Fzd1 is one receptor present in the Müllerian duct mesenchyme and could be the putative receptor for beta-catenin activation in the Müllerian duct. In summary, our findings suggest that mesenchymal beta-catenin is a downstream effector of Wnt7a that mediates the patterning of the oviduct and proper differentiation of the uterus.
Deutscher
Erica
E
Department of Veterinary Biosciences, 3806 VMBSB, 2001 South Lincoln Avenue, University of Illinois, Urbana, IL 61802, USA.
Hung-Chang Yao
Humphrey
H
D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D017931:DNA Primers / Q000235:genetics; D005187:Fallopian Tubes / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D005260:Female; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D008648:Mesoderm / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009095:Mullerian Ducts / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism*; D010641:Phenotype; D011247:Pregnancy; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D018000:Receptors, Peptide / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta; D014599:Uterus / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D051153:Wnt Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000071818:Wnt-5a Protein; D051176:beta Catenin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
C495267:CTNNB1 protein, mouse; D017931:DNA Primers; D051157:Frizzled Receptors; C489739:Fzd1 protein, mouse; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; C490508:Wnt7a protein, mouse; C084621:anti-Mullerian hormone receptor; D051176:beta Catenin