title: Molecular characterization of the ventricular conduction system in the developing mouse heart: topographical correlation in normal and congenitally malformed hearts.
abstract: OBJECTIVE
  Within the adult heart, it is convention to distinguish the conduction system and working (atrial and ventricular) myocardium. The adult conduction system (CS) comprises the sinoatrial (SAN), and atrioventricular (AVN) nodes, the atrioventricular bundle (AVB), the bundle branches and the peripheral Purkinje fibers, each of which display distinct functional properties and distinct profile of gene expression. Characterization of the mouse cardiac conduction system during development is rudimentary at present, even though genetically-modified mice are an increasing source of information regarding cardiac function and embryonic heart development.
  
  
  METHODS
  We have performed a detailed study of the pattern of expression of myosin heavy chain (MHC), myosin light chain (MLC), troponin I (TnI) isoforms, connexin 43 (Cx43), desmin and alpha-smooth muscle actin (alpha-SMA), in the ventricular conduction system of normal and congenitally malformed mouse hearts (iv background) from embryonic day 14.5 to 19.5.
  
  
  RESULTS
  The AVN is characterized by co-expression of MHC and MLC isoforms and no detectable expression of Cx43, desmin or alpha-SMA. The AVB expresses betaMHC and MLC2v, but no alphaMHC, MLC2a, Cx43, desmin or alpha-SMA. The right and left bundle branches display enhanced expression of desmin and alpha-SMA but no Cx43. The normal expression profile is maintained in congenitally malformed hearts such as double-outlet right ventricle and common atrioventricular canal. Three-dimensional reconstruction of the conduction system shows normal arrangement of the bundle branches in congenitally malformed hearts, but abnormal location and/or extension of the AVN.
  
  
  CONCLUSIONS
  Molecular characterization allows to follow the development of the CS in both, normal and malformed mouse hearts. Normal phenotypic expression of the CS is independent of heart situs but shows minor modifications in the presence of heart malformations. It is concluded that the AVN derives from the atrioventricular canal myocardium, the bundle of His from the ventricular myocardium, and the bundle branches from the ventricular trabeculations. Our results do not provide evidence to support an extra-cardiac origin of the ventricular CS.
authors.affiliation: Department of Experimental Biology, Faculty of Experimental and Health Sciences, University of Jaén, Paraje Las Lagunillas s/n, 23071, Jaén, Spain. dfranco@ujaen.es
authors.forename: D
authors.initials: D
authors.lastname: Franco
authors.forename: J M
authors.initials: JM
authors.lastname: Icardo
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001283:Atrioventricular Node / Q000196:embryology / Q000378:metabolism; D002036:Bundle of His / Q000196:embryology / Q000378:metabolism; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D003893:Desmin / Q000235:genetics / Q000378:metabolism; D005865:Gestational Age; D006325:Heart Atria / Q000196:embryology / Q000378:metabolism; D006329:Heart Conduction System / Q000196:embryology* / Q000378:metabolism; D006330:Heart Defects, Congenital / Q000196:embryology* / Q000378:metabolism; D006352:Heart Ventricles / Q000196:embryology / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008817:Mice, Mutant Strains; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D018994:Myosin Light Chains / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012849:Sinoatrial Node / Q000196:embryology / Q000378:metabolism; D019210:Troponin I / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D018031:Connexin 43; D003893:Desmin; D018994:Myosin Light Chains; D020033:Protein Isoforms; D012333:RNA, Messenger; D019210:Troponin I; D018995:Myosin Heavy Chains