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

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 du...

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Autores principales:	Teresa Elo, Päivi H. Lindfors, Qiang Lan, Maria Voutilainen, Ewelina Trela, Claes Ohlsson, Sung-Ho Huh, David M. Ornitz, Matti Poutanen, Beatrice A. Howard, Marja L. Mikkola
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5ba55031e3954d0bbbb781c3f97f48b6
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spelling	oai:doaj.org-article:5ba55031e3954d0bbbb781c3f97f48b62021-12-02T12:32:04ZEctodysplasin target gene Fgf20 regulates mammary bud growth and ductal invasion and branching during puberty10.1038/s41598-017-04637-12045-2322https://doaj.org/article/5ba55031e3954d0bbbb781c3f97f48b62017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04637-1https://doaj.org/toc/2045-2322Abstract 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.Teresa EloPäivi H. LindforsQiang LanMaria VoutilainenEwelina TrelaClaes OhlssonSung-Ho HuhDavid M. OrnitzMatti PoutanenBeatrice A. HowardMarja L. MikkolaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Teresa Elo Päivi H. Lindfors Qiang Lan Maria Voutilainen Ewelina Trela Claes Ohlsson Sung-Ho Huh David M. Ornitz Matti Poutanen Beatrice A. Howard Marja L. Mikkola Ectodysplasin target gene Fgf20 regulates mammary bud growth and ductal invasion and branching during puberty
description	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.
format	article
author	Teresa Elo Päivi H. Lindfors Qiang Lan Maria Voutilainen Ewelina Trela Claes Ohlsson Sung-Ho Huh David M. Ornitz Matti Poutanen Beatrice A. Howard Marja L. Mikkola
author_facet	Teresa Elo Päivi H. Lindfors Qiang Lan Maria Voutilainen Ewelina Trela Claes Ohlsson Sung-Ho Huh David M. Ornitz Matti Poutanen Beatrice A. Howard Marja L. Mikkola
author_sort	Teresa Elo
title	Ectodysplasin target gene Fgf20 regulates mammary bud growth and ductal invasion and branching during puberty
title_short	Ectodysplasin target gene Fgf20 regulates mammary bud growth and ductal invasion and branching during puberty
title_full	Ectodysplasin target gene Fgf20 regulates mammary bud growth and ductal invasion and branching during puberty
title_fullStr	Ectodysplasin target gene Fgf20 regulates mammary bud growth and ductal invasion and branching during puberty
title_full_unstemmed	Ectodysplasin target gene Fgf20 regulates mammary bud growth and ductal invasion and branching during puberty
title_sort	ectodysplasin target gene fgf20 regulates mammary bud growth and ductal invasion and branching during puberty
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5ba55031e3954d0bbbb781c3f97f48b6
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_version_	1718394158928887808

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

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