title: FGF10/FGFR2b signaling is essential for cardiac fibroblast development and growth of the myocardium.
abstract: The epicardium serves as a source of growth factors that regulate myocardial proliferation and as a source of epicardial-derived cells (EPDC), which give rise to interstitial cardiac fibroblasts and perivascular cells. These progenitors populate the compact myocardium to become part of the mature coronary vasculature and fibrous skeleton of the heart. Little is known about the mechanisms that regulate EPDC migration into the myocardium or the functions carried out by these cells once they enter the myocardium. However, it has been proposed that cardiac fibroblasts are important for growth of the heart during late gestation and are a source of homeostatic factors in the adult. Here, we identify a myocardial to epicardial fibroblast growth factor (FGF) signal, mediated by FGF10 and FGFR2b, that is essential for movement of cardiac fibroblasts into the compact myocardium. Inactivation of this signaling pathway results in fewer epicardial derived cells within the compact myocardium, decreased myocardial proliferation and a resulting smaller thin-walled heart.
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Mónica
authors.initials: M
authors.lastname: Vega-Hernández
authors.forename: Attila
authors.initials: A
authors.lastname: Kovacs
authors.forename: Stijn
authors.initials: S
authors.lastname: De Langhe
authors.forename: David M
authors.initials: DM
authors.lastname: Ornitz
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D051526:Fibroblast Growth Factor 10 / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000033:anatomy & histology / Q000196:embryology* / Q000254:growth & development*; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000166:cytology*; D038081:Organogenesis / Q000502:physiology; D010496:Pericardium / Q000166:cytology / Q000502:physiology; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D051497:Receptor, Fibroblast Growth Factor, Type 2