Spatiotemporal pattern of commitment to slowed proliferation in the embryonic mouse heart indicates progressive differentiation of the cardiac conduction system.

Patterns of DNA synthesis in the developing mouse heart between ED7.5-18.5 were studied by a combination of thymidine and bromodeoxyuridine labeling techniques. From earliest stages, we found zones of slow myocyte proliferation at both the venous and arterial poles of the heart, as well as in the atrioventricular region. The labeling index was distinctly higher in nonmyocardial populations (endocardium, epicardium, and cardiac cushions). Ventricular trabeculae showed lower proliferative activity than the ventricular compact layer after their appearance at ED9.5. Low labeling was observed in the pectinate muscles of the atria from ED11.5. The His bundle, bundle branches, and Purkinje fiber network likewise were distinguished by their lack of labeling. Thymidine birthdating (label dilution) showed that the cells in these emerging components of the cardiac conduction system terminally differentiated between ED8.5-13.5. These patterns of slowed proliferation correlate well with those in other species, and can serve as a useful marker for the forming conduction system.

[1]  David Sedmera,et al.  Development of the cardiac pacemaking and conduction system. , 2003, Birth defects research. Part C, Embryo today : reviews.

[2]  S. Rivkees,et al.  Neuregulin-1 promotes formation of the murine cardiac conduction system , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[3]  David Sedmera,et al.  Cellular changes in experimental left heart hypoplasia , 2002, The Anatomical record.

[4]  M. Buckingham,et al.  The anterior heart-forming field: voyage to the arterial pole of the heart. , 2002, Trends in genetics : TIG.

[5]  S. Kubalak,et al.  Elevated transforming growth factor beta2 enhances apoptosis and contributes to abnormal outflow tract and aortic sac development in retinoic X receptor alpha knockout embryos. , 2002, Development.

[6]  A. Juraszek,et al.  A GATA-6 gene heart-region-specific enhancer provides a novel means to mark and probe a discrete component of the mouse cardiac conduction system , 2001, Mechanisms of Development.

[7]  M. Buckingham,et al.  The arterial pole of the mouse heart forms from Fgf10-expressing cells in pharyngeal mesoderm. , 2001, Developmental cell.

[8]  M. Yacoub,et al.  Elevated expression of Nkx‐2.5 in developing myocardial conduction cells , 2001, The Anatomical record.

[9]  M Delmar,et al.  Null Mutation of Connexin43 Causes Slow Propagation of Ventricular Activation in the Late Stages of Mouse Embryonic Development , 2001, Circulation research.

[10]  J Jalife,et al.  Visualization and functional characterization of the developing murine cardiac conduction system. , 2001, Development.

[11]  D. Franco,et al.  Molecular characterization of the ventricular conduction system in the developing mouse heart: topographical correlation in normal and congenitally malformed hearts. , 2001, Cardiovascular research.

[12]  J. Franciosi,et al.  FGF-2-induced imbalance in early embryonic heart cell proliferation: a potential cause of late cardiovascular anomalies. , 2000, Teratology.

[13]  W. R. Giles,et al.  Voltage-Sensitive Dye Mapping of Activation and Conduction in Adult Mouse Hearts , 2000, Annals of Biomedical Engineering.

[14]  K W Hewett,et al.  The rate and anisotropy of impulse propagation in the postnatal terminal crest are correlated with remodeling of Cx43 gap junction pattern. , 2000, Cardiovascular research.

[15]  R. P. Thompson,et al.  Development of the cardiac conduction system involves recruitment within a multipotent cardiomyogenic lineage. , 1999, Development.

[16]  W H Lamers,et al.  Development of the cardiac conduction system. , 1998, Circulation research.

[17]  A. Moorman,et al.  Patterns of expression in the developing myocardium: towards a morphologically integrated transcriptional model. , 1998, Cardiovascular research.

[18]  R. P. Thompson,et al.  Expression of homeobox genes Msx‐1 (Hox‐7) and Msx‐2 (Hox‐8) during cardiac development in the chick , 1993, Developmental dynamics : an official publication of the American Association of Anatomists.

[19]  C. Green,et al.  Evidence for a distinct gap-junctional phenotype in ventricular conduction tissues of the developing and mature avian heart. , 1993, Circulation research.

[20]  W H Lamers,et al.  Persisting zones of slow impulse conduction in developing chicken hearts. , 1992, Circulation research.

[21]  T. Mikawa,et al.  Clonal analysis of cardiac morphogenesis in the chicken embryo using a replication‐defective retrovirus: I. Formation of the ventricular myocardium , 1992, Developmental dynamics : an official publication of the American Association of Anatomists.

[22]  R. P. Thompson,et al.  Cell Differentiation Birthdates in the Embryonic Rat Heart a , 1990 .

[23]  J. A. Los,et al.  The local expression of adult chicken heart myosins during development , 1986, Anatomy and Embryology.

[24]  Y. Satow,et al.  Morphogenesis of human cardiac outflow , 1985, The Anatomical record.

[25]  T. P. Fitzharris,et al.  Morphogenesis of the truncus arteriosus of the chick embryo heart: tissue reorganization during septation. , 1979, The American journal of anatomy.

[26]  I. Cameron,et al.  Cell proliferation patterns during cytodifferentiation in embryonic chick tissues: liver, heart and erythrocytes. , 1971, Journal of embryology and experimental morphology.

[27]  D. Grohmann Mitotische Wachstumsintensität des embryonalen und fetalen Hühnchenherzens und ihre Bedeutung für die Entstehung von Herzmissbildungen , 2004, Zeitschrift für Zellforschung und Mikroskopische Anatomie.

[28]  J. A. Los,et al.  Isomyosin expression patterns in tubular stages of chicken heart development: a 3-D immunohistochemical analysis , 2004, Anatomy and Embryology.

[29]  J. Skepper,et al.  Comparison of connexin expression patterns in the developing mouse heart and human foetal heart , 2004, Molecular and Cellular Biochemistry.

[30]  David Sedmera,et al.  The oldest, toughest cells in the heart. , 2003, Novartis Foundation symposium.

[31]  José Jalife,et al.  Null Mutation of Connexin 43 Causes Slow Propagation of Ventricular Activation in the Late Stages of Mouse Embryonic Development , 2001 .

[32]  N. Severs,et al.  Connexin45 (alpha 6) expression delineates an extended conduction system in the embryonic and mature rodent heart. , 1999, Developmental genetics.

[33]  T. Mikawa,et al.  Conducting the embryonic heart: orchestrating development of specialized cardiac tissues. , 1999, Trends in cardiovascular medicine.

[34]  D. Grohmann [Mitotic growth potential of embryonic and fetal chicken hearts and its significance for the understanding of heart malformations]. , 1961, Zeitschrift fur Zellforschung und mikroskopische Anatomie.