Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 750K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sengbusch, J. K. Articles by Yang, J. T. Search for Related Content PubMed PubMed Citation Articles by Sengbusch, J. K. Articles by Yang, J. T. Social Bookmarking                            What's this?

© The Rockefeller University Press, 0021-9525/2002/5/873 $5.00
The Journal of Cell Biology, Volume 157, Number 5, May 28, 2002 873-882

Dual functions of 4ß1 integrin in epicardial development

Jennifer K. Sengbusch, Wei He, Karen A. Pinco and Joy T. Yang

Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205

Address correspondence to Joy T. Yang, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. Tel.: (410) 614-5938. Fax: (410) 955-4129. E-mail: jyang{at}jhmi.edu

The epicardium of the mammalian heart arises from progenitor cells outside the developing heart. The epicardial progenitor (EPP) cells migrate onto the heart through a cyst-mediated mechanism in which the progenitors are released from the tissue of origin as cysts; the cysts float in the fluid of the pericardial cavity and attach to the naked myocardial surface of the heart, and cells in the cysts then migrate out to form an epithelial sheet. In this paper, we show that the gene encoding the 4 subunit of 4ß1 integrin (4ß1) is essential for this migratory process. We have generated a knockin mutation in mice replacing the 4 integrin gene with the lacZ reporter gene, placing lacZ under the control of the 4 integrin promoter. We show that in homozygous mutant embryos, the migration of EPP progenitor cells is impaired due to inefficient budding of the cysts and a failure of the cells in the cysts to migrate on the heart. This study provides direct genetic evidence for essential roles for 4ß1 integrin–mediated cell adhesion in the migration of progenitor cells to form the epicardium, in addition to a previous finding that 4ß1 is essential for maintaining the epicardium (Yang, J.T., H. Rayburn, and R.O. Hynes. 1995. Development. 121:549–560).

Key Words: integrins; cell migration; heart; epicardium; mouse development

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Aitsebaomo, J., Portbury, A. L., Schisler, J. C., Patterson, C. (2008). Brothers and Sisters: Molecular Insights Into Arterial-Venous Heterogeneity. Circ. Res. 103: 929-939 [Abstract] [Full Text]  
• Goldfinger, L. E., Tzima, E., Stockton, R., Kiosses, W. B., Kinbara, K., Tkachenko, E., Gutierrez, E., Groisman, A., Nguyen, P., Chien, S., Ginsberg, M. H. (2008). Localized {alpha}4 Integrin Phosphorylation Directs Shear Stress-Induced Endothelial Cell Alignment. Circ. Res. 103: 177-185 [Abstract] [Full Text]  
• Feral, C. C., Neels, J. G., Kummer, C., Slepak, M., Olefsky, J. M., Ginsberg, M. H. (2008). Blockade of {alpha}4 Integrin Signaling Ameliorates the Metabolic Consequences of High-Fat Diet-Induced Obesity. Diabetes 57: 1842-1851 [Abstract] [Full Text]  
• Dikeman, D. A., Rivera Rosado, L. A., Horn, T. A., Alves, C. S., Konstantopoulos, K., Yang, J. T. (2008). {alpha}4{beta}1-Integrin regulates directionally persistent cell migration in response to shear flow stimulation. Am. J. Physiol. Cell Physiol. 295: C151-C159 [Abstract] [Full Text]  
• Schubert, S. W., Lamoureux, N., Kilian, K., Klein-Hitpass, L., Hashemolhosseini, S. (2008). Identification of Integrin-{alpha}4, Rb1, and Syncytin A as Murine Placental Target Genes of the Transcription Factor GCMa/Gcm1. J. Biol. Chem. 283: 5460-5465 [Abstract] [Full Text]  
• Compton, L. A., Potash, D. A., Brown, C. B., Barnett, J. V. (2007). Coronary Vessel Development Is Dependent on the Type III Transforming Growth Factor {beta} Receptor. Circ. Res. 101: 784-791 [Abstract] [Full Text]  
• Majesky, M. W. (2007). Developmental Basis of Vascular Smooth Muscle Diversity. Arterioscler. Thromb. Vasc. Bio. 27: 1248-1258 [Abstract] [Full Text]  
• Kirschner, K. M., Wagner, N., Wagner, K.-D., Wellmann, S., Scholz, H. (2006). The Wilms Tumor Suppressor Wt1 Promotes Cell Adhesion through Transcriptional Activation of the {alpha}4integrin Gene. J. Biol. Chem. 281: 31930-31939 [Abstract] [Full Text]  
• Hirose, T., Karasawa, M., Sugitani, Y., Fujisawa, M., Akimoto, K., Ohno, S., Noda, T. (2006). PAR3 is essential for cyst-mediated epicardial development by establishing apical cortical domains. Development 133: 1389-1398 [Abstract] [Full Text]  
• Merki, E., Zamora, M., Raya, A., Kawakami, Y., Wang, J., Zhang, X., Burch, J., Kubalak, S. W., Kaliman, P., Belmonte, J. C. I., Chien, K. R., Ruiz-Lozano, P. (2005). From the Cover: Epicardial retinoid X receptor {alpha} is required for myocardial growth and coronary artery formation. Proc. Natl. Acad. Sci. USA 102: 18455-18460 [Abstract] [Full Text]  
• Hsia, D. A., Lim, S.-T., Bernard-Trifilo, J. A., Mitra, S. K., Tanaka, S., den Hertog, J., Streblow, D. N., Ilic, D., Ginsberg, M. H., Schlaepfer, D. D. (2005). Integrin {alpha}4{beta}1 Promotes Focal Adhesion Kinase-Independent Cell Motility via {alpha}4 Cytoplasmic Domain-Specific Activation of c-Src. Mol. Cell. Biol. 25: 9700-9712 [Abstract] [Full Text]  
• Mu, H., Ohashi, R., Lin, P., Yao, Q., Chen, C. (2005). Cellular and molecular mechanisms of coronary vessel development. Vasc Med 10: 37-44 [Abstract]  
• Muramatsu, H., Zou, P., Suzuki, H., Oda, Y., Chen, G.-Y., Sakaguchi, N., Sakuma, S., Maeda, N., Noda, M., Takada, Y., Muramatsu, T. (2004). {alpha}4{beta}1- and {alpha}6{beta}1-integrins are functional receptors for midkine, a heparin-binding growth factor. J. Cell Sci. 117: 5405-5415 [Abstract] [Full Text]  
• Watt, A. J., Battle, M. A., Li, J., Duncan, S. A. (2004). GATA4 is essential for formation of the proepicardium and regulates cardiogenesis. Proc. Natl. Acad. Sci. USA 101: 12573-12578 [Abstract] [Full Text]  
• Wada, A. M., Willet, S. G., Bader, D. (2003). Coronary Vessel Development: A Unique Form of Vasculogenesis. Arterioscler. Thromb. Vasc. Bio. 23: 2138-2145 [Abstract] [Full Text]  
• Luttun, A., Carmeliet, P. (2003). De novo vasculogenesis in the heart. Cardiovasc Res 58: 378-389 [Abstract] [Full Text]  
• Pinco, K. A., He, W., Yang, J. T. (2002). alpha 4beta 1 Integrin Regulates Lamellipodia Protrusion via a Focal Complex/Focal Adhesion-independent Mechanism. Mol. Biol. Cell 13: 3203-3217 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents