Reconstruction of the Patterns of Gene Expression in the Developing Mouse Heart Reveals an Architectural Arrangement That Facilitates the Understanding of Atrial Malformations and Arrhythmias

Firm knowledge about the formation of the atrial components and of the variations seen in congenital cardiac malformations and abnormal atrial rhythms is fundamental to our understanding of the normal structure of the definitive atrial chambers. The atrial region is relatively inaccessible and has c...

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Bibliographic Details
Published in:Circulation Research 2004-12, Vol.95 (12), p.1207-1215
Main Authors: Soufan, Alexandre T, van den Hoff, Maurice J.B, Ruijter, Jan M, de Boer, Piet A.J, Hagoort, Jaco, Webb, Sandra, Anderson, Robert H, Moorman, Antoon F.M
Format: Article
Language:English
Subjects:
Animals
Atrial Appendage - embryology
Atrial Appendage - metabolism
Atrial Natriuretic Factor
Biological and medical sciences
Cardiac dysrhythmias
Cardiology. Vascular system
Connexins - analysis
Connexins - biosynthesis
Connexins - genetics
Fetal Heart - anatomy & histology
Fetal Heart - metabolism
Fundamental and applied biological sciences. Psychology
Gap Junction alpha-5 Protein
Gene Expression Regulation, Developmental
Gestational Age
Heart
Heart Atria - embryology
Heart Atria - metabolism
Heart Conduction System - embryology
Medical sciences
Mesoderm - ultrastructure
Mice
Models, Anatomic
Myocardium - chemistry
Myocardium - cytology
Myocardium - metabolism
Natriuretic Peptide, C-Type - analysis
Natriuretic Peptide, C-Type - biosynthesis
Natriuretic Peptide, C-Type - genetics
Protein Precursors - analysis
Protein Precursors - biosynthesis
Protein Precursors - genetics
Pulmonary Veins - embryology
Pulmonary Veins - metabolism
Staining and Labeling
Tachycardia, Ectopic Atrial - embryology
Tachycardia, Ectopic Atrial - etiology
Tachycardia, Ectopic Atrial - pathology
Vertebrates: cardiovascular system
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Description
Summary:Firm knowledge about the formation of the atrial components and of the variations seen in congenital cardiac malformations and abnormal atrial rhythms is fundamental to our understanding of the normal structure of the definitive atrial chambers. The atrial region is relatively inaccessible and has continued to be the source of disagreement. Seeking to resolve these controversies, we made three-dimensional reconstructions of the myocardial components of the developing atrium, identifying domains on the basis of differential expression of myocardial markers, connexin40, and natriuretic precursor peptide A. These reconstructions, made from serial sections of mouse embryos, show that from the outset of atrial development, the systemic and pulmonary veins are directly connected to the atrium. Relative to the systemic junctions, however, the pulmonary venous junction appears later. Our experience shows that three-dimensional reconstructions have three advantages. First, they provide clear access to the combined morphological and molecular data, allowing clarification and verification of morphogenetic concepts for nonmorphological experts and setting the scene for further discussion. Second, they demonstrate that, from the outset, the myocardium surrounding the pulmonary veins is distinct from that clothing the systemic venoatrial junctions. Third, they reveal an anatomical and molecular continuity between the entrance of the systemic venous tributaries, the internodal atrial myocardium, and the atrioventricular region. All these regions are derived from primary myocardium, providing a molecular basis for the observed nonrandom distribution of focal right atrial tachycardias.
ISSN:0009-7330
1524-4571
1524-4539
DOI:10.1161/01.RES.0000150852.04747.e1