title: Chamber formation and morphogenesis in the developing mammalian heart.
abstract: In this study we challenge the generally accepted view that cardiac chambers form from an array of segmental primordia arranged along the anteroposterior axis of the linear and looping heart tube. We traced the spatial pattern of expression of genes encoding atrial natriuretic factor, sarcoplasmic reticulum calcium ATPase, Chisel, Irx5, Irx4, myosin light chain 2v, and beta-myosin heavy chain and related these to morphogenesis. Based on the patterns we propose a two-step model for chamber formation in the embryonic heart. First, a linear heart forms, which is composed of "primary" myocardium that nonetheless shows polarity in phenotype and gene expression along its anteroposterior and dorsoventral axes. Second, specialized ventricular chamber myocardium is specified at the ventral surface of the linear heart tube, while distinct left and right atrial myocardium forms more caudally on laterodorsal surfaces. The process of looping aligns these primordial chambers such that they face the outer curvature. Myocardium of the inner curvature, as well as that of inflow tract, atrioventricular canal, and outflow tract, retains the molecular signature originally found in linear heart tube myocardium. Evidence for distinct transcriptional programs which govern compartmentalization in the forming heart is seen in the patterns of expression of Hand1 for the dorsoventral axis, Irx4 and Tbx5 for the anteroposterior axis, and Irx5 for the distinction between primary and chamber myocardium.
authors.affiliation: Department of Anatomy & Embryology, Academic Medical Center, University of Amsterdam, Amsterdam, 1105, The Netherlands.
authors.forename: V M
authors.initials: VM
authors.lastname: Christoffels
authors.forename: P E
authors.initials: PE
authors.lastname: Habets
authors.forename: D
authors.initials: D
authors.lastname: Franco
authors.forename: M
authors.initials: M
authors.lastname: Campione
authors.forename: F
authors.initials: F
authors.lastname: de Jong
authors.forename: W H
authors.initials: WH
authors.lastname: Lamers
authors.forename: Z Z
authors.initials: ZZ
authors.lastname: Bao
authors.forename: S
authors.initials: S
authors.lastname: Palmer
authors.forename: C
authors.initials: C
authors.lastname: Biben
authors.forename: R P
authors.initials: RP
authors.lastname: Harvey
authors.forename: A F
authors.initials: AF
authors.lastname: Moorman
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000302:isolation & purification; D051792:Basic Helix-Loop-Helix Proteins; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000302:isolation & purification; D018031:Connexin 43 / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000235:genetics / Q000302:isolation & purification; D006325:Heart Atria / Q000196:embryology*; D006352:Heart Ventricles / Q000196:embryology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000302:isolation & purification; D017403:In Situ Hybridization; D008954:Models, Biological; D008961:Models, Structural; D009024:Morphogenesis / Q000235:genetics; D009218:Myosins / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics / Q000302:isolation & purification; D014158:Transcription, Genetic
chemical_list: D009320:Atrial Natriuretic Factor; D051792:Basic Helix-Loop-Helix Proteins; D000252:Calcium-Transporting ATPases; D018031:Connexin 43; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009218:Myosins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D014157:Transcription Factors; C097341:helix-loop-helix protein, eHAND