Trabecular myocytes of the embryonic heart require N-cadherin for migratory unit identity.

The myocardial wall of the vertebrate heart changes from a simple epithelium to a trabeculated structure during embryogenesis. This process occurs when epithelioid cardiomyocytes migrate toward the endocardium, which we show is coincident with up-regulation of the cell adhesion molecule, N-cadherin. To study the role of N-cadherin expressed at the trabeculation stage, a replication-defective retrovirus expressing a dominant negative mutant of N-cadherin (delta N-cadherin) was engineered. Control viruses were designed to express beta-galactosidase or a full-length N-cadherin. Viruses were introduced into epithelioid presumptive myocytes at the time they initiate the epithelial-mesenchymal transformation. Individual cells infected with control viruses generated daughter myocytes which migrated toward endocardium as a tight cluster, thereby generating a clone that forms a single or at most two trabeculae. In contrast, myocytes expressing delta N-cadherin were sparsely distributed within the myocardium and failed to form the ridge-shaped clone. Thus, in addition to its known roles in myocyte epithelialization and intercalated disc formation, N-cadherin appears to play a role in homotypic interactions between nonepithelial migratory myocytes during trabecular formation of the embryonic heart.

[1]  M. Takeichi,et al.  Neural crest cell-cell adhesion controlled by sequential and subpopulation-specific expression of novel cadherins. , 1995, Development.

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

[3]  K. Linask.  N-cadherin localization in early heart development and polar expression of Na+,K(+)-ATPase, and integrin during pericardial coelom formation and epithelialization of the differentiating myocardium. , 1992, Developmental biology.

[4]  E. Rodriguez-Boulan,et al.  Polarized release of enveloped viruses in the embryonic chick heart: demonstration of epithelial polarity in the presumptive myocardium. , 1990, Developmental biology.

[5]  J. Rossant,et al.  fgfr-1 is required for embryonic growth and mesodermal patterning during mouse gastrulation. , 1994, Genes & development.

[6]  A. P. Soler,et al.  N-cadherin involvement in cardiac myocyte interaction and myofibrillogenesis. , 1994, Developmental biology.

[7]  E. Clark,et al.  Developmental Cardiology: Morphogenesis and Function , 1990 .

[8]  L. Cohen-Gould,et al.  Expression of sarcomeric myosin in the presumptive myocardium of chicken embryos occurs within six hours of myocyte commitment , 1992, Developmental dynamics : an official publication of the American Association of Anatomists.

[9]  Rüdiger Klein,et al.  Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor , 1995, Nature.

[10]  Z. Kam,et al.  The involvement of adherens junction components in myofibrillogenesis in cultured cardiac myocytes. , 1992, Development.

[11]  K. Yutzey,et al.  Expression of the atrial-specific myosin heavy chain AMHC1 and the establishment of anteroposterior polarity in the developing chicken heart. , 1994, Development.

[12]  H. Eppenberger,et al.  N-cadherin in adult rat cardiomyocytes in culture. I. Functional role of N-cadherin and impairment of cell-cell contact by a truncated N-cadherin mutant. , 1996, Journal of cell science.

[13]  C. Gregory,et al.  P-cadherin and E-cadherin are co-expressed in MDCK cells. , 1993, Biochemical and biophysical research communications.

[14]  V. Hamburger,et al.  A series of normal stages in the development of the chick embryo. 1951. , 2012, Developmental dynamics : an official publication of the American Association of Anatomists.

[15]  M. Takeichi,et al.  Spatial and temporal expression pattern of N-cadherin cell adhesion molecules correlated with morphogenetic processes of chicken embryos. , 1987, Developmental biology.

[16]  T. Mikawa,et al.  Retroviral vectors to study cardiovascular development. , 1996, Trends in cardiovascular medicine.

[17]  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.

[18]  C. Kintner.  Regulation of embryonic cell adhesion by the cadherin cytoplasmic domain , 1992, Cell.

[19]  T. Mikawa.  Retroviral Targeting of FGF and FGFR in Cardiomyocytes and Coronary Vascular Cells during Heart Development a , 1995, Annals of the New York Academy of Sciences.

[20]  Kuo-Fen Lee,et al.  Requirement for neuregulin receptor erbB2 in neural and cardiac development , 1995, Nature.

[21]  F. Manasek,et al.  Embryonic development of the heart. I. A light and electron microscopic study of myocardial development in the early chick embryo , 1968, Journal of morphology.

[22]  K. Linask,et al.  N-cadherin-catenin interaction: necessary component of cardiac cell compartmentalization during early vertebrate heart development. , 1997, Developmental biology.

[23]  M. Sacristán,et al.  T‐Cadherin 2: Molecular characterization, function in cell adhesion, and coexpression with T‐cadherin and N‐cadherin , 1993, Journal of neuroscience research.

[24]  R. P. Thompson,et al.  Dissociated spatial patterning of gap junctions and cell adhesion junctions during postnatal differentiation of ventricular myocardium. , 1997, Circulation research.

[25]  M. K. Byeon,et al.  NCAM polypeptides in heart development: association with Z discs of forms that contain the muscle-specific domain , 1995, The Journal of cell biology.

[26]  E. Koller,et al.  Differential Targeting of T- and N-cadherin in Polarized Epithelial Cells* , 1996, The Journal of Biological Chemistry.

[27]  B. Ranscht,et al.  T-cadherin, a novel cadherin cell adhesion molecule in the nervous system lacks the conserved cytoplasmic region , 1991, Neuron.

[28]  H. Temin,et al.  High mutation rate of a spleen necrosis virus-based retrovirus vector , 1986, Molecular and cellular biology.

[29]  L. Theill,et al.  Neuregulins with an Ig-like domain are essential for mouse myocardial and neuronal development. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[30]  V. García-Martínez,et al.  Primitive-streak origin of the cardiovascular system in avian embryos. , 1993, Developmental Biology.

[31]  T. Mikawa,et al.  Clonal analysis of cardiac morphogenesis in the chicken embryo using a replication‐defective retrovirus. III: Polyclonal origin of adjacent ventricular myocytes , 1992, Developmental dynamics : an official publication of the American Association of Anatomists.

[32]  T. Mikawa,et al.  The polyclonal origin of myocyte lineages. , 1996, Annual review of physiology.

[33]  T. Mikawa,et al.  Terminal diversification of the myocyte lineage generates Purkinje fibers of the cardiac conduction system. , 1995, Development.

[34]  M. Takeichi,et al.  Cadherin cell adhesion receptors as a morphogenetic regulator. , 1991, Science.

[35]  M. Labow,et al.  Defective development of the embryonic and extraembryonic circulatory systems in vascular cell adhesion molecule (VCAM-1) deficient mice. , 1995, Development.

[36]  T. Mikawa,et al.  Retroviral analysis of cardiac morphogenesis: discontinuous formation of coronary vessels. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[37]  R. Hynes,et al.  Developmental defects in mouse embryos lacking N-cadherin. , 1997, Developmental biology.