Hostname: page-component-586b7cd67f-t7czq Total loading time: 0 Render date: 2024-11-26T15:20:01.476Z Has data issue: false hasContentIssue false
  • English
  • Français

Expression of Discoidin Domain Receptor 2 (DDR2) in the Developing Heart

Published online by Cambridge University Press:  12 May 2005

Mary O. Morales ,
Robert L. Price  and
Edie C. Goldsmith
Mary O. Morales
Affiliation:
Department of Cell and Developmental Biology & Anatomy, University of South Carolina School of Medicine, Columbia, SC 29209, USA
Robert L. Price
Affiliation:
Department of Cell and Developmental Biology & Anatomy, University of South Carolina School of Medicine, Columbia, SC 29209, USA
Edie C. Goldsmith
Affiliation:
Department of Cell and Developmental Biology & Anatomy, University of South Carolina School of Medicine, Columbia, SC 29209, USA
Get access

Abstract

Interactions between cells and the surrounding extracellular matrix are important for a number of developmental events. In the heart, cardiac fibroblasts produce the majority of extracellular matrix proteins, particularly collagen types I and III. Cells originating from the proepicardial organ migrate over the surface of the heart, invade the underlying myocardium and ultimately give rise to smooth muscle cells, fibroblasts, and coronary endothelium. Although integrin expression in the developing heart has been well characterized, the expression of Discoidin Domain Receptor 2 (DDR2) remains to be defined. Using confocal microscopy, the expression of DDR2 was examined at several points during cardiac development. Initially, DDR2 expression was detected on the epicardial surface of the heart and on endothelial and mesenchymal cells within the cardiac cushions. As development progressed, DDR2 expression increased at localized regions in the apex and atrioventricular sulcus, although this expression decreased from epicardial to endocardial surface. Eventually, DDR2 expression spanned the myocardial free wall and was detected within the septum. Not until postnatal development was DDR2 expression detected uniformly throughout the myocardium and this distribution was maintained in the adult heart. In summary, the data presented demonstrate that the distribution of DDR2-positive cells changes within the heart during development.

Keywords

discoidin domain receptorcollagenreceptor tyrosine kinaseextracellular matrixfibroblast
Type
Research Article
Information
Microscopy and Microanalysis , Volume 11 , Issue 3 , June 2005 , pp. 260 - 267
Copyright
© 2005 Microscopy Society of America

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Agarwal, G., Kovac, L., Radziejewski, C., & Samuelsson, J.J. (2002). Binding of discoidin domain receptor 2 to collagen I: An atomic force microscopy investigation. Biochemistry, published on-line in ASAP alerts.Google Scholar
Alves, F., Vogel, W., Mossie, K., Millauer, B., Hofler, H., & Ullrich, A. (1995). Distinct structural characteristics of discoidin I subfamily receptor tyrosine kinases and complementary expression in human cancer. Oncogene 10, 609–618.Google Scholar
Benjamin, I.J., Jalil, J.E., Tan, L.B., Cho, K., Weber, T.K., & Clark, W.A. (1989). Isoproterenol-induced myocardial fibrosis in relation to myocyte necrosis. Circ Res 65, 657–670.Google Scholar
Borg, T.K. (1982). Development of the connective tissue network in the neonatal hamster heart. Am J Anat 165, 435–443.Google Scholar
Borg, T.K. & Caulfield, J.B. (1979). Collagen in the heart. Texas Rep Biol Med 39, 321–333.Google Scholar
Borg, T.K., Rubin, K., Lundgren, E., Borg, K., & Obrink, B. (1984). Recognition of extracellular matrix components by neonatal and adult cardiac myocytes. Dev Biol 104, 86–96.Google Scholar
Chin, G.S., Lee, S., Hsu, M., Liu, W., Kim, W.J.H., Levinson, H., & Longaker, M.T. (2001). Discoidin domain receptors and their ligand, collagen, are temporally regulated in fetal rat fibroblasts in vitro. Plast Reconstr Surg 107, 769–776.Google Scholar
Dettman, R.W., Denetclaw, W., Ordahl, C.P., & Bristow, J. (1998). Common epicardial origin of coronary vascular smooth muscle, perivascular fibroblasts, and intermyocardial fibroblasts in the avian heart. Dev Biol 193, 169–181.Google Scholar
Gittenberger-de Groot, A.C., Vrancken Peeters, M.P.F.M., Mentink, M.M.T., Gourdie, R.G., & Poelmann, R.E. (1998). Epicardium-derived cells contribute a novel population to the myocardial wall and the atrioventricular cushions. Circ Res 82, 1043–1052.Google Scholar
Goldsmith, E.C., Hoffman, A., Morales, M.O., Potts, J.D., Price, R.L., McFadden, A., Rice, M., & Borg, T.K. (2004). Organization of fibroblasts in the heart. Dev Dyn 230, 787–794.Google Scholar
Johnson, J.D., Edman, J.C., & Rutter, W.J. (1993). A receptor tyrosine kinase found in breast carcinoma cells has an extracellular discoidin I-like domain. Proc Natl Acad Sci USA 90, 5677–5681.Google Scholar
Labrador, J.P., Azcoitia, V., Tuckermann, J., Lin, C., Olaso, E., Manes, S., Bruckner, K., Goergen, J.L., Lemke, G., Yancopoulos, G., Angel, P., Matrinez-A, C., & Klein, R. (2001). The collagen receptor DDR2 regulates proliferation and its elimination leads to dwarfism. EMBO Rep 2, 446–452.Google Scholar
Lai, C. & Lemke, G. (1991). An extended family of protein-tyrosine kinase genes differentially expressed in the vertebrate nervous system. Neuron 6, 691–704.Google Scholar
Lai, C. & Lemke, G. (1994). Structure and expression of the Tyro 10 receptor tyrosine kinase. Oncogene 9, 877–883.Google Scholar
Leitinger, B. (2003). Molecular analysis of collagen binding by the human discoidin domain receptors, DDR1 and DDR2: Identification of collagen binding sites in DDR2. J Biol Chem 278, 16761–16769.Google Scholar
Lemmon, M.A. & Schlessinger, J. (1994). Regulation of signal transduction and signal diversity by receptor oligomerization. Trends Biochem Sci 19, 459–463.Google Scholar
Markwald, R.R., Runyan, R.B., Kitten, G.T., Funderburg, F.M., Bernanke, D.H., & Bauer, P.R. (1984). Use of collagen gel cultures to study heart development: Proteoglycan and glycoprotein interactions during the formation of endocardial cushions tissue. In The Role of Extracellular Matrix in Development, Trelstand, R.L. (Ed.), pp. 323–350. New York: Alan R. Liss Press.
Olaso, E., Ikeda, K., Eng, F.J., Xu, L., Wang, L., Lin, H.C., & Friedman, S.L. (2001). DDR2 receptor promotes MMP-2-mediated proliferation and invasion by hepatic stellate cells. J Clin Invest 108, 1369–1378.Google Scholar
Olaso, E., Labrador, P., Wang, L., Ikeda, K., Eng, F.J., Klein, R., Lovett, D.H., Lin, H.C., & Friedman, S.L. (2002). DDR2 receptor regulates fibroblast proliferation and migration through extracellular matrix in association with transcriptional activation of MMP-2. J Biol Chem 277, 3606–3613.Google Scholar
Ross, R.S. & Borg, T.K. (2001). Integrins and the myocardium. Circ Res 88, 1112–1119.Google Scholar
Schlessinger, J. (1997). Direct binding and activation of receptor tyrosine kinases by collagen. Cell 91, 869–872.Google Scholar
Shrivastava, A., Radziejewski, C., Campbell, E., Kovac, L., McGlynn, M., Ryan, T.E., Davis, S., Goldfarb, M.P., Glass, D.J., Lemke, G., & Yancopoulos, G.D. (1997). An orphan receptor tyrosine kinase family whose members serve as non-integrin collagen receptors. Mol Cell 1, 25–34.Google Scholar
Sinning, A.R., Lepera, R.C., & Markwald, R.R. (1988). Initial expression of type I procollagen in chick cardiac mesenchyme is dependent upon myocardial stimulation. Dev Biol 130, 167–174.Google Scholar
Vogel, W., Gish, G.D., Alves, F., & Pawson, T. (1997). The discoidin domain receptor tyrosine kinases are activated by collagen. Mol Cell 1, 13–23.Google Scholar
Weber, K.T. (1989). Cardiac interstitium in health and disease: The fibrillar collagen network. J Am Coll Cardiol 13, 1637–1652.Google Scholar