title: Developmental origin, growth, and three-dimensional architecture of the atrioventricular conduction axis of the mouse heart.
abstract: BACKGROUND
  The clinically important atrioventricular conduction axis is structurally complex and heterogeneous, and its molecular composition and developmental origin are uncertain.
  
  
  OBJECTIVE
  To assess the molecular composition and 3D architecture of the atrioventricular conduction axis in the postnatal mouse heart and to define the developmental origin of its component parts.
  
  
  RESULTS
  We generated an interactive 3D model of the atrioventricular junctions in the mouse heart using the patterns of expression of Tbx3, Hcn4, Cx40, Cx43, Cx45, and Nav1.5, which are important for conduction system function. We found extensive figure-of-eight rings of nodal and transitional cells around the mitral and tricuspid junctions and in the base of the atrial septum. The rings included the compact node and nodal extensions. We then used genetic lineage labeling tools (Tbx2(+/Cre), Mef2c-AHF-Cre, Tbx18(+/Cre)), along with morphometric analyses, to assess the developmental origin of the specific components of the axis. The majority of the atrial components, including the atrioventricular rings and compact node, are derived from the embryonic atrioventricular canal. The atrioventricular bundle, including the lower cells of the atrioventricular node, in contrast, is derived from the ventricular myocardium. No contributions to the conduction system myocardium were identified from the sinus venosus, the epicardium, or the dorsal mesenchymal protrusion.
  
  
  CONCLUSIONS
  The atrioventricular conduction axis comprises multiple domains with distinctive molecular signatures. The atrial part proliferates from the embryonic atrioventricular canal, along with myocytes derived from the developing atrial septum. The atrioventricular bundle and lower nodal cells are derived from ventricular myocardium.
authors.affiliation: Heart Failure Research Center, Academic Medical Center, University of Amsterdam, the Netherlands.
authors.forename: Wim T J
authors.initials: WT
authors.lastname: Aanhaanen
authors.forename: Mathilda T M
authors.initials: MT
authors.lastname: Mommersteeg
authors.forename: Julia
authors.initials: J
authors.lastname: Norden
authors.forename: Vincent
authors.initials: V
authors.lastname: Wakker
authors.forename: Corrie
authors.initials: C
authors.lastname: de Gier-de Vries
authors.forename: Robert H
authors.initials: RH
authors.lastname: Anderson
authors.forename: Andreas
authors.initials: A
authors.lastname: Kispert
authors.forename: Antoon F M
authors.initials: AF
authors.lastname: Moorman
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Christoffels
mesh_terms: D000818:Animals; D001283:Atrioventricular Node / Q000033:anatomy & histology / Q000196:embryology / Q000254:growth & development; D005260:Female; D006321:Heart / Q000033:anatomy & histology / Q000196:embryology / Q000254:growth & development; D006329:Heart Conduction System / Q000033:anatomy & histology / Q000196:embryology* / Q000254:growth & development*; D007091:Image Processing, Computer-Assisted / Q000379:methods; D021621:Imaging, Three-Dimensional; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy