title: Ectodysplasin/NF-κB Promotes Mammary Cell Fate via Wnt/β-catenin Pathway.
abstract: Mammary gland development commences during embryogenesis with the establishment of a species typical number of mammary primordia on each flank of the embryo. It is thought that mammary cell fate can only be induced along the mammary line, a narrow region of the ventro-lateral skin running from the axilla to the groin. Ectodysplasin (Eda) is a tumor necrosis factor family ligand that regulates morphogenesis of several ectodermal appendages. We have previously shown that transgenic overexpression of Eda (K14-Eda mice) induces formation of supernumerary mammary placodes along the mammary line. Here, we investigate in more detail the role of Eda and its downstream mediator transcription factor NF-κB in mammary cell fate specification. We report that K14-Eda mice harbor accessory mammary glands also in the neck region indicating wider epidermal cell plasticity that previously appreciated. We show that even though NF-κB is not required for formation of endogenous mammary placodes, it is indispensable for the ability of Eda to induce supernumerary placodes. A genome-wide profiling of Eda-induced genes in mammary buds identified several Wnt pathway components as potential transcriptional targets of Eda. Using an ex vivo culture system, we show that suppression of canonical Wnt signalling leads to a dose-dependent inhibition of supernumerary placodes in K14-Eda tissue explants.
authors.affiliation: Developmental Biology Program, Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Maria
authors.initials: M
authors.lastname: Voutilainen
authors.affiliation: Developmental Biology Program, Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Päivi H
authors.initials: PH
authors.lastname: Lindfors
authors.affiliation: Developmental Biology Program, Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Trela
authors.affiliation: Developmental Biology Program, Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Darielle
authors.initials: D
authors.lastname: Lönnblad
authors.affiliation: Developmental Biology Program, Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Vera
authors.initials: V
authors.lastname: Shirokova
authors.affiliation: Developmental Biology Program, Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Teresa
authors.initials: T
authors.lastname: Elo
authors.affiliation: Developmental Biology Program, Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Elisa
authors.initials: E
authors.lastname: Rysti
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Schmidt-Ullrich
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Schneider
authors.affiliation: Developmental Biology Program, Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Marja L
authors.initials: ML
authors.lastname: Mikkola
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D053331:Ectodysplasins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D018859:Hair Follicle / Q000254:growth & development; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology / Q000254:growth & development*; D051379:Mice; D009024:Morphogenesis / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics*
chemical_list: D053331:Ectodysplasins; D016328:NF-kappa B