title: FGF ligands of the postnatal mammary stroma regulate distinct aspects of epithelial morphogenesis.
abstract: FGF signaling is essential for mammary gland development, yet the mechanisms by which different members of the FGF family control stem cell function and epithelial morphogenesis in this tissue are not well understood. Here, we have examined the requirement of Fgfr2 in mouse mammary gland morphogenesis using a postnatal organ regeneration model. We found that tissue regeneration from basal stem cells is a multistep event, including luminal differentiation and subsequent epithelial branching morphogenesis. Basal cells lacking Fgfr2 did not generate an epithelial network owing to a failure in luminal differentiation. Moreover, Fgfr2 null epithelium was unable to undergo ductal branch initiation and elongation due to a deficiency in directional migration. We identified FGF10 and FGF2 as stromal ligands that control distinct aspects of mammary ductal branching. FGF10 regulates branch initiation, which depends on directional epithelial migration. By contrast, FGF2 controls ductal elongation, requiring cell proliferation and epithelial expansion. Together, our data highlight a pleiotropic role of Fgfr2 in stem cell differentiation and branch initiation, and reveal that different FGF ligands regulate distinct aspects of epithelial behavior.
authors: Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors: Xiaohong
authors: X
authors: Zhang
authors: Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors: Denisse
authors: D
authors: Martinez
authors: Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors: Zuzana
authors: Z
authors: Koledova
authors: Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors: Guijuan
authors: G
authors: Qiao
authors: Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors: Charles H
authors: CH
authors: Streuli
authors: Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK paul.pf.lu@gmail.com.
authors: Pengfei
authors: P
authors: Lu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D016764:Cell Polarity / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D004848:Epithelium / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D005260:Female; D051526:Fibroblast Growth Factor 10 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008024:Ligands; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009024:Morphogenesis / Q000187:drug effects / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000172:deficiency / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D051526:Fibroblast Growth Factor 10; D008024:Ligands; D016222:Fibroblast Growth Factor 2; D019869:Phosphatidylinositol 3-Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D020929:Mitogen-Activated Protein Kinase Kinases; D020782:Matrix Metalloproteinases
keywords: Branching morphogenesis; Breast; Collective epithelial migration; FGF10; FGFR2; Fibroblast growth factor; Mammary gland; Stem cell