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Ectodysplasin/NF-κB promotes mammary cell fate via Wnt/β-catenin pathway

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Item Type:Article
Title:Ectodysplasin/NF-κB promotes mammary cell fate via Wnt/β-catenin pathway
Creators Name:Voutilainen, M. and Lindfors, P.H. and Trela, E. and Loennblad, D. and Shirokova, V. and Elo, T. and Rysti, E. and Schmidt-Ullrich, R. and Schneider, P. and Mikkola, M.L.
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-{kappa}B 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-{kappa}B 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.
Keywords:Cell Differentiation, Developmental Gene Expression Regulation, Ectodysplasins, Hair Follicle, Human Mammary Glands, Mammalian Embryo, Morphogenesis, NF-{kappa} B, Wnt Signaling Pathway, Animals, Mice
Source:PLoS Genetics
ISSN:1553-7404
Publisher:Public Library of Science (U.S.A.)
Volume:11
Number:11
Page Range:e1005676
Date:18 November 2015
Official Publication:https://doi.org/10.1371/journal.pgen.1005676
PubMed:View item in PubMed

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