QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, W. E. I. Articles by Lo, C. W. Search for Related Content PubMed PubMed Citation Articles by Li, W. E. I. Articles by Lo, C. W.

An essential role for connexin43 gap junctions in mouse coronary artery development

¹ Biology Department, Goddard Laboratories, University of Pennsylvania, Philadelphia, PA, USA
² Division of Neonatology, Department of Pediatrics, Duke University, Durham, NC, USA
³ Laboratory of Developmental Biology, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
⁴ Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, SC, USA
⁵ Department of Medicine, University of Pennsylvania Medical School, Philadelphia, PA, USA

*Author for correspondence (e-mail: clo{at}nhlbi.nih.gov)

Accepted 24 January 2002

Connexin43 knockout mice die neonatally from conotruncal heart malformation and outflow obstruction. Previous studies have indicated the involvement of neural crest perturbations in these cardiac anomalies. We provide evidence for the involvement of another extracardiac cell population, the proepicardial cells. These cells give rise to the vascular smooth muscle cells of the coronary arteries and cardiac fibroblasts in the heart. We have observed the abnormal presence of fibroblast and vascular smooth muscle cells in the infundibular pouches of the connexin43 knockout mouse heart. In addition, the connexin43 knockout mice exhibit a variety of coronary artery patterning defects previously described for neural crest-ablated chick embryos, such as anomalous origin of the coronary arteries, absent left or right coronary artery, and accessory coronary arteries. However, we show that proepicardial cells also express connexin43 gap junctions abundantly. The proepicardial cells are functionally well coupled, and this coupling is significantly reduced with the loss of connexin43 function. Further analysis revealed an elevation in the speed of cell locomotion and cell proliferation rate in the connexin43-deficient proepicardial cells. A parallel analysis of proepicardial cells in transgenic mice with dominant negative inhibition of connexin43 targeted only to neural crest cells showed none of these coupling, proliferation or migration changes. These mice exhibit outflow obstruction, but no infundibular pouches. Together these findings indicate an important role for connexin43 in coronary artery patterning, a role that probably involves the proepicardial and cardiac neural crest cells. We discuss the potential involvement of connexin43 in human cardiovascular anomalies involving the coronary arteries.

Key words: Connexin43, Gap junctions, Coronary artery, Cell proliferation, Cell migration, Proepicardial cell

This article has been cited by other articles:

				C.-J. Wei, R. Francis, X. Xu, and C. W. Lo Connexin43 Associated with an N-cadherin-containing Multiprotein Complex Is Required for Gap Junction Formation in NIH3T3 Cells J. Biol. Chem., May 20, 2005; 280(20): 19925 - 19936. [Abstract] [Full Text] [PDF]

				W. Li, E. L. Hertzberg, and D. C. Spray Regulation of Connexin43-Protein Binding in Astrocytes in Response to Chemical Ischemia/Hypoxia J. Biol. Chem., March 4, 2005; 280(9): 7941 - 7948. [Abstract] [Full Text] [PDF]

				D. A. Iacobas, S. Iacobas, W. E. I. Li, G. Zoidl, R. Dermietzel, and D. C. Spray Genes controlling multiple functional pathways are transcriptionally regulated in connexin43 null mouse heart Physiol Genomics, February 10, 2005; 20(3): 211 - 223. [Abstract] [Full Text] [PDF]

				C. J. Hatcher, N. Y.S.-G. Diman, M.-S. Kim, D. Pennisi, Y. Song, M. M. Goldstein, T. Mikawa, and C. T. Basson A role for Tbx5 in proepicardial cell migration during cardiogenesis Physiol Genomics, July 8, 2004; 18(2): 129 - 140. [Abstract] [Full Text] [PDF]

				S. Poelzing, F. G. Akar, E. Baron, and D. S. Rosenbaum Heterogeneous connexin43 expression produces electrophysiological heterogeneities across ventricular wall Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H2001 - H2009. [Abstract] [Full Text] [PDF]

				D. A. Iacobas, M. Urban-Maldonado, S. Iacobas, E. Scemes, and D. C. Spray Array analysis of gene expression in connexin-43 null astrocytes Physiol Genomics, November 11, 2003; 15(3): 177 - 190. [Abstract] [Full Text] [PDF]