title: GATA-Binding Factor 6 Contributes to Atrioventricular Node Development and Function.
abstract: BACKGROUND
  Several transcription factors regulate cardiac conduction system (CCS) development and function but the role of each in specifying distinct CCS components remains unclear. GATA-binding factor 6 (GATA6) is a zinc-finger transcription factor that is critical for patterning the cardiovascular system. However, the role of GATA6 in the embryonic heart and CCS has never been shown.
  
  
  RESULTS
  We report that Gata6 is expressed abundantly in the proximal CCS during midgestation in mice. Myocardial-specific deletion of the carboxyl zinc-finger of Gata6 induces loss of hyperpolarizing cyclic nucleotide-gated channel, subtype 4 staining in the compact atrioventricular node with some retention of hyperpolarizing cyclic nucleotide-gated channel, subtype 4 staining in the atrioventricular bundle, but has no significant effect on the connexin-40-positive bundle branches. Furthermore, myocardial-specific deletion of the carboxyl zinc-finger of Gata6 alters atrioventricular conduction in postnatal life as assessed by surface and invasive electrophysiological evaluation, as well as decreasing the number of ventricular myocytes and inducing compensatory myocyte hypertrophy. Myocardial-specific deletion of the carboxyl zinc-finger of Gata6 is also associated with downregulation of the transcriptional repressor ID2 and the cardiac sodium-calcium exchanger NCX1 in the proximal CCS, where GATA6 transactivates both of these factors. Finally, carboxyl zinc-finger deletion of Gata6 reduces cell-cycle exit of TBX3+ myocytes in the developing atrioventricular bundle during the period of atrioventricular node specification, which results in fewer TBX3+ cells in the proximal CCS of mature mutant mice.
  
  
  CONCLUSIONS
  GATA6 contributes to the development and postnatal function of the murine atrioventricular node by promoting cell-cycle exit of specified cardiomyocytes toward a conduction system lineage.
authors.affiliation: From the Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia (F.L., M.M.L., N.N.P., K.J.S., T.W.); and Department of Physiology, Section of Clinical Cardiac Electrophysiology & Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (V.V.P.).
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: From the Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia (F.L., M.M.L., N.N.P., K.J.S., T.W.); and Department of Physiology, Section of Clinical Cardiac Electrophysiology & Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (V.V.P.).
authors.forename: Min Min
authors.initials: MM
authors.lastname: Lu
authors.affiliation: From the Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia (F.L., M.M.L., N.N.P., K.J.S., T.W.); and Department of Physiology, Section of Clinical Cardiac Electrophysiology & Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (V.V.P.).
authors.forename: Neil N
authors.initials: NN
authors.lastname: Patel
authors.affiliation: From the Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia (F.L., M.M.L., N.N.P., K.J.S., T.W.); and Department of Physiology, Section of Clinical Cardiac Electrophysiology & Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (V.V.P.).
authors.forename: Kurt J
authors.initials: KJ
authors.lastname: Schillinger
authors.affiliation: From the Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia (F.L., M.M.L., N.N.P., K.J.S., T.W.); and Department of Physiology, Section of Clinical Cardiac Electrophysiology & Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (V.V.P.).
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: From the Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia (F.L., M.M.L., N.N.P., K.J.S., T.W.); and Department of Physiology, Section of Clinical Cardiac Electrophysiology & Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (V.V.P.). vickas.patel@temple.edu.
authors.forename: Vickas V
authors.initials: VV
authors.lastname: Patel
mesh_terms: D000818:Animals; D001283:Atrioventricular Node / Q000196:embryology*; D050993:GATA6 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*
chemical_list: D050993:GATA6 Transcription Factor; C494760:Gata6 protein, mouse
keywords: GATA6 transcription factor; atrioventricular node; cardiac electrophysiology