Published online before print November 18, 2004, doi: 10.1161/01.RES.0000150852.04747.e1
© 2004 American Heart Association, Inc.
Integrative Physiology |
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
From the Experimental and Molecular Cardiology Group (A.T.S., M.J.B.v.d.H., J.M.R., P.A.J.d.B., J.H., A.F.M.M), Academic Medical Centre, University of Amsterdam, The Netherlands; The Department of Basic Medical Sciences (S.W.), Anatomy and Developmental Biology, St Georges Medical School, London, UK; and the Cardiac Unit (R.H.A.), Institute of Child Health, University College London, London, UK.
Correspondence to Prof Dr Antoon F.M. Moorman, Department of Anatomy and Embryology, Academic Medical Centre, Meibergdreef 15, 1105AZ Amsterdam, The Netherlands. E-mail a.f.moorman{at}amc.uva.nl
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.
Key Words: internodal tracts • phenotyping • dorsal mesocardium • conduction system
This article has been cited by other articles:
 |
|
 |
|
  S. M. Savolainen, J. F. Foley, and S. A. Elmore Histology Atlas of the Developing Mouse Heart with Emphasis on E11.5 to E18.5 Toxicol Pathol, June 1, 2009; 37(4): 395 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Goddeeris, S. Rho, A. Petiet, C. L. Davenport, G. A. Johnson, E. N. Meyers, and J. Klingensmith Intracardiac septation requires hedgehog-dependent cellular contributions from outside the heart Development, May 15, 2008; 135(10): 1887 - 1895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Jones, M. Yamamoto, J. O. Tellez, R. Billeter, M. R. Boyett, H. Honjo, and M. K. Lancaster Distinguishing Properties of Cells From the Myocardial Sleeves of the Pulmonary Veins: A Comparison of Normal and Abnormal Pacemakers Circ Arrhythmia Electrophysiol, April 1, 2008; 1(1): 39 - 48. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Torban, A.-M. Patenaude, S. Leclerc, S. Rakowiecki, S. Gauthier, G. Andelfinger, D. J. Epstein, and P. Gros Genetic interaction between members of the Vangl family causes neural tube defects in mice PNAS, March 4, 2008; 105(9): 3449 - 3454. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T.M. Mommersteeg, N. A. Brown, O. W.J. Prall, C. de Gier-de Vries, R. P. Harvey, A. F.M. Moorman, and V. M. Christoffels Pitx2c and Nkx2-5 Are Required for the Formation and Identity of the Pulmonary Myocardium Circ. Res., October 26, 2007; 101(9): 902 - 909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Reggiani, D. Raciti, R. Airik, A. Kispert, and A. W. Brandli The prepattern transcription factor Irx3 directs nephron segment identity Genes & Dev., September 15, 2007; 21(18): 2358 - 2370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F.M Moorman, V. M Christoffels, R. H Anderson, and M. J.B van den Hoff The heart-forming fields: one or multiple? Phil Trans R Soc B, August 29, 2007; 362(1484): 1257 - 1265. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T.M. Mommersteeg, W. M.H. Hoogaars, O. W.J. Prall, C. de Gier-de Vries, C. Wiese, D. E.W. Clout, V. E. Papaioannou, N. A. Brown, R. P. Harvey, A. F.M. Moorman, et al. Molecular Pathway for the Localized Formation of the Sinoatrial Node Circ. Res., February 16, 2007; 100(3): 354 - 362. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T.M. Mommersteeg, A. T. Soufan, F. J. de Lange, M. J.B. van den Hoff, R. H. Anderson, V. M. Christoffels, and A. F.M. Moorman Two Distinct Pools of Mesenchyme Contribute to the Development of the Atrial Septum Circ. Res., August 18, 2006; 99(4): 351 - 353. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. M. Christoffels, M. T.M. Mommersteeg, M.-O. Trowe, O. W.J. Prall, C. de Gier-de Vries, A. T. Soufan, M. Bussen, K. Schuster-Gossler, R. P. Harvey, A. F.M. Moorman, et al. Formation of the Venous Pole of the Heart From an Nkx2-5-Negative Precursor Population Requires Tbx18 Circ. Res., June 23, 2006; 98(12): 1555 - 1563. [Abstract] [Full Text] [PDF]
|
|