Ectodysplasin target gene Fgf20 regulates mammary bud growth and ductal invasion and branching during puberty

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Elo , T , Lindfors , P H , Lan , Q , Voutilainen , M , Trela , E , Ohlsson , C , Huh , S-H , Ornitz , D M , Poutanen , M , Howard , B A & Mikkola , M L 2017 , ' Ectodysplasin target gene Fgf20 regulates mammary bud growth and ductal invasion and branching during puberty ' , Scientific Reports , vol. 7 , 5049 . https://doi.org/10.1038/s41598-017-04637-1

Title: Ectodysplasin target gene Fgf20 regulates mammary bud growth and ductal invasion and branching during puberty
Author: Elo, Teresa; Lindfors, Paivi H.; Lan, Qiang; Voutilainen, Maria; Trela, Ewelina; Ohlsson, Claes; Huh, Sung-Ho; Ornitz, David M.; Poutanen, Matti; Howard, Beatrice A.; Mikkola, Marja L.
Contributor: University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
Date: 2017-07-11
Number of pages: 13
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/232837
Abstract: Mammary gland development begins with the appearance of epithelial placodes that invaginate, sprout, and branch to form small arborized trees by birth. The second phase of ductal growth and branching is driven by the highly invasive structures called terminal end buds (TEBs) that form at ductal tips at the onset of puberty. Ectodysplasin (Eda), a tumor necrosis factor-like ligand, is essential for the development of skin appendages including the breast. In mice, Eda regulates mammary placode formation and branching morphogenesis, but the underlying molecular mechanisms are poorly understood. Fibroblast growth factor (Fgf) receptors have a recognized role in mammary ductal development and stem cell maintenance, but the ligands involved are ill-defined. Here we report that Fgf20 is expressed in embryonic mammary glands and is regulated by the Eda pathway. Fgf20 deficiency does not impede mammary gland induction, but compromises mammary bud growth, as well as TEB formation, ductal outgrowth and branching during puberty. We further show that loss of Fgf20 delays formation of Eda-induced supernumerary mammary buds and normalizes the embryonic and postnatal hyperbranching phenotype of Eda overexpressing mice. These findings identify a hitherto unknown function for Fgf20 in mammary budding and branching morphogenesis.
Subject: HYPOHIDROTIC ECTODERMAL DYSPLASIA
ESTROGEN-RECEPTOR-ALPHA
GLAND DEVELOPMENT
SIGNALING PATHWAY
STEM-CELL
KAPPA-B
MORPHOGENESIS
MOUSE
AMPHIREGULIN
ACTIVATION
3122 Cancers
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