PMID:15621532

Citation	Lavine, KJ, Yu, K, White, AC, Zhang, X, Smith, C, Partanen, J and Ornitz, DM (2005) Endocardial and epicardial derived FGF signals regulate myocardial proliferation and differentiation in vivo. Dev. Cell 8:85-95
Abstract	The epicardium regulates growth and survival of the underlying myocardium. This activity depends on intrinsic retinoic acid (RA) and erythropoietin signals. However, these signals do not act directly on the myocardium and instead are proposed to regulate the production of an unidentified soluble epicardial derived mitogen. Here, we show that Fgf9, Fgf16, and Fgf20 are expressed in the endocardium and epicardium and that RA can induce epicardial expression of Fgf9. Using knockout mice and an embryonic heart organ culture system, we show that endocardial and epicardial derived FGF signals regulate myocardial proliferation during midgestation heart development. We further show that this FGF signal is received by both FGF receptors 1 and 2 acting redundantly in the cardiomyoblast. In the absence of this signal, premature differentiation results in cellular hypertrophy and newborn mice develop a dilated cardiomyopathy. FGFs thus constitute all or part of the epicardial signal regulating myocardial growth and differentiation.
Links	PubMed Online version:10.1016/j.devcel.2004.12.002
Keywords	Age Factors; Animals; Bromodeoxyuridine/metabolism; Cell Count/methods; Cell Differentiation/drug effects; Cell Differentiation/physiology; Cell Proliferation/drug effects; Cell Proliferation/radiation effects; Embryo, Mammalian; Fibroblast Growth Factor 9; Fibroblast Growth Factors/classification; Fibroblast Growth Factors/deficiency; Fibroblast Growth Factors/genetics; Fibroblast Growth Factors/metabolism; Fibroblast Growth Factors/physiology; Gene Expression Regulation, Developmental/drug effects; Gene Expression Regulation, Developmental/physiology; Heart/embryology; Immunohistochemistry/methods; In Situ Hybridization/methods; Mice; Mice, Knockout; Microscopy, Electron, Transmission/methods; Myocardium/metabolism; Myocardium/ultrastructure; Organ Culture Techniques/methods; RNA, Messenger/biosynthesis; Receptors, Fibroblast Growth Factor/metabolism; Reverse Transcriptase Polymerase Chain Reaction/methods; Signal Transduction/physiology; Tretinoin/pharmacology
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