title: Ror2 regulates branching, differentiation, and actin-cytoskeletal dynamics within the mammary epithelium.
abstract: Wnt signaling encompasses β-catenin-dependent and -independent networks. How receptor context provides Wnt specificity in vivo to assimilate multiple concurrent Wnt inputs throughout development remains unclear. Here, we identified a refined expression pattern of Wnt/receptor combinations associated with the Wnt/β-catenin-independent pathway in mammary epithelial subpopulations. Moreover, we elucidated the function of the alternative Wnt receptor Ror2 in mammary development and provided evidence for coordination of this pathway with Wnt/β-catenin-dependent signaling in the mammary epithelium. Lentiviral short hairpin RNA (shRNA)-mediated depletion of Ror2 in vivo increased branching and altered the differentiation of the mammary epithelium. Microarray analyses identified distinct gene level alterations within the epithelial compartments in the absence of Ror2, with marked changes observed in genes associated with the actin cytoskeleton. Modeling of branching morphogenesis in vitro defined specific defects in cytoskeletal dynamics accompanied by Rho pathway alterations downstream of Ror2 loss. The current study presents a model of Wnt signaling coordination in vivo and assigns an important role for Ror2 in mammary development.
authors.affiliation: Department of Molecular and Cellular Biology and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030.
authors.forename: Kevin
authors.initials: K
authors.lastname: Roarty
authors.affiliation: Department of Molecular and Cellular Biology and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030.
authors.forename: Amy N
authors.initials: AN
authors.lastname: Shore
authors.affiliation: Department of Molecular and Cellular Biology and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030.
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Creighton
authors.affiliation: Department of Molecular and Cellular Biology and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030 jrosen@bcm.edu.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Rosen
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D048430:Cell Shape; D004847:Epithelial Cells / Q000502:physiology*; D004848:Epithelium / Q000502:physiology; D005260:Female; D008321:Mammary Glands, Animal / Q000166:cytology / Q000502:physiology*; D051379:Mice; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000502:physiology*; D060449:Wnt Signaling Pathway
chemical_list: D057050:Receptor Tyrosine Kinase-like Orphan Receptors; C477010:Ror2 protein, mouse