Lineage and morphogenetic analysis of the cardiac valves.
We used a genetic lineage-labeling system to establish the material contributions of the progeny of 3 specific cell types to the cardiac valves. Thus, we labeled irreversibly the myocardial (alphaMHC-Cre+), endocardial (Tie2-Cre+), and neural crest (Wnt1-Cre+) cells during development and assessed their eventual contribution to the definitive valvar complexes. The leaflets and tendinous cords of the mitral and tricuspid valves, the atrioventricular fibrous continuity, and the leaflets of the outflow tract valves were all found to be generated from mesenchyme derived from the endocardium, with no substantial contribution from cells of the myocardial and neural crest lineages. Analysis of chicken-quail chimeras revealed absence of any substantial contribution from proepicardially derived cells. Molecular and morphogenetic analysis revealed several new aspects of atrioventricular valvar formation. Marked similarities are seen during the formation of the mural leaflets of the mitral and tricuspid valves. These leaflets form by protrusion and growth of a sheet of atrioventricular myocardium into the ventricular lumen, with subsequent formation of valvar mesenchyme on its surface rather than by delamination of lateral cushions from the ventricular myocardial wall. The myocardial layer is subsequently removed by the process of apoptosis. In contrast, the aortic leaflet of the mitral valve, the septal leaflet of the tricuspid valve, and the atrioventricular fibrous continuity between these valves develop from the mesenchyme of the inferior and superior atrioventricular cushions. The tricuspid septal leaflet then delaminates from the muscular ventricular septum late in development.
Experimental and Molecular Cardiology Group, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Frederik J
FJ
de Lange
Antoon F M
AF
Moorman
Robert H
RH
Anderson
Jörg
J
Männer
Alexandre T
AT
Soufan
Corrie
C
de Gier-de Vries
Michael D
MD
Schneider
Sandra
S
Webb
Maurice J B
MJ
van den Hoff
Vincent M
VM
Christoffels
D000818:Animals; D017209:Apoptosis; D019070:Cell Lineage; D002465:Cell Movement; D002642:Chick Embryo; D002678:Chimera / Q000196:embryology; D002815:Chordae Tendineae / Q000166:cytology / Q000196:embryology; D003370:Coturnix / Q000196:embryology; D004699:Endocardium / Q000166:cytology*; D005318:Fetal Heart / Q000166:cytology; D017930:Genes, Reporter; D005865:Gestational Age; D006351:Heart Valves / Q000166:cytology / Q000196:embryology*; D021621:Imaging, Three-Dimensional; D019426:Integrases / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D008943:Mitral Valve / Q000166:cytology / Q000196:embryology; D009024:Morphogenesis; D009206:Myocardium / Q000166:cytology; D009432:Neural Crest / Q000166:cytology; D042787:Receptor, TIE-2 / Q000235:genetics; D017384:Sequence Deletion; D014261:Tricuspid Valve / Q000166:cytology / Q000196:embryology; D014764:Viral Proteins / Q000235:genetics; D051153:Wnt Proteins; D051155:Wnt1 Protein
D036341:Intercellular Signaling Peptides and Proteins; D014764:Viral Proteins; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D042787:Receptor, TIE-2; C045073:Cre recombinase; D019426:Integrases