title: FGF signaling enforces cardiac chamber identity in the developing ventricle.
abstract: Atrial and ventricular cardiac chambers behave as distinct subunits with unique morphological, electrophysiological and contractile properties. Despite the importance of chamber-specific features, chamber fate assignments remain relatively plastic, even after differentiation is underway. In zebrafish, Nkx transcription factors are essential for the maintenance of ventricular characteristics, but the signaling pathways that operate upstream of Nkx factors in this context are not well understood. Here, we show that FGF signaling plays an essential part in enforcing ventricular identity. Loss of FGF signaling results in a gradual accumulation of atrial cells, a corresponding loss of ventricular cells, and the appearance of ectopic atrial gene expression within the ventricle. These phenotypes reflect important roles for FGF signaling in promoting ventricular traits, both in early-differentiating cells that form the initial ventricle and in late-differentiating cells that append to its arterial pole. Moreover, we find that FGF signaling functions upstream of Nkx genes to inhibit ectopic atrial gene expression. Together, our data suggest a model in which sustained FGF signaling acts to suppress cardiomyocyte plasticity and to preserve the integrity of the ventricular chamber.
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Arjana
authors.identifier: 0000-0002-4119-6121
authors.initials: A
authors.lastname: Pradhan
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Xin-Xin I
authors.identifier: 0000-0002-2707-7759
authors.initials: XI
authors.lastname: Zeng
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Pragya
authors.identifier: 0000-0002-5292-6740
authors.initials: P
authors.lastname: Sidhwani
authors.affiliation: Developmental Genetics Program and Department of Cell Biology, Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Sara R
authors.identifier: 0000-0002-5869-2260
authors.initials: SR
authors.lastname: Marques
authors.affiliation: Division of Cardiology, Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Vanessa
authors.identifier: 0000-0003-1990-4651
authors.initials: V
authors.lastname: George
authors.affiliation: Division of Cardiology, Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Kimara L
authors.identifier: 0000-0002-6066-6002
authors.initials: KL
authors.lastname: Targoff
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Neil C
authors.identifier: 0000-0003-2324-3796
authors.initials: NC
authors.lastname: Chi
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA dyelon@ucsd.edu.
authors.forename: Deborah
authors.identifier: 0000-0003-3523-4053
authors.initials: D
authors.lastname: Yelon
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006325:Heart Atria / Q000166:cytology; D006352:Heart Ventricles / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013997:Time Factors; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D029961:Zebrafish Proteins; D005346:Fibroblast Growth Factors
keywords: Amhc; Atrium; Nkx2.5; Ventricle; Vmhc; Zebrafish