Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

A homologue of Drosophila tissue polarity gene frizzled is expressed in migrating myofibroblasts in the infarcted rat heart

Abstract

Myocardial infarction results in the formation of granulation tissue in the injured ventricular wall. This tissue contains myofibroblasts in highly organized arrays; their contractile properties may help to prevent the infarct area from dilatation. The mechanisms that control myofibroblast alignment are unknown. We found that myofibroblasts express a homologue of Drosophila tissue polarity gene frizzled (fz2) when migrating into the granulation tissue. The expression is decreased after the cells have aligned. This suggests that fz2 is involved in the spatial control of cardiac wound repair after infarction, possibly through intra- and inter-cellular transmission of polarity signals as in developing Drosophila. Mutations in the fz2 gene may impair myofibroblast alignment in the infarct area, thereby resulting in ventricular dilatation and aneurism following infarction.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Willems, I.E.M.G. et al. The a-smooth muscle actin-positive cells in healing human myocardial scars. Am. J Pathol. 145, 868–875 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Sun, Y. et al. Cardiac angiotensin converting enzyme and myocardial fibrosis in the rat. Cardiovasc Res. 28, 1423–1432 (1994).

    Article  CAS  PubMed  Google Scholar 

  3. Cleutjens, J.P.M. et al. Collagen remodeling after myocardial infarction in the rat heart. Am J Pathol. 147, 325–338 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Vracko, R. & Thorning, D. Contractile cells in rat myocardial scar tissue. Lab Invest. 65, 214–227 (1991).

    CAS  PubMed  Google Scholar 

  5. Schmitt-Graf, A., Desmouliere, A. & Gabbiani, G. Heterogeneity of myofibroblast phenotypic features: An example of fibroblastic cell plasticity. Virchows Arch. 425, 3–24 (1994).

    Article  Google Scholar 

  6. Gaudron, P. et al. Progressive left ventricular dysfunction and remodeling after myocardial infarction. Circulations 87, 755–763 (1993).

    Article  CAS  Google Scholar 

  7. Blankesteijn, W.M. et al. Increased expression of a homologue of Drosophila tissue polarity gene ‘frizzled’ in left ventricular hypertrophy in the rat, as determined by subtractive hybridization. J Mol Cell Cardiol. 28, 1187–1191 (1996).

    Article  CAS  PubMed  Google Scholar 

  8. Adler, P.N. The genetic control of tissue polarity in Drosophila. BioEssays 14, 735–741 (1992).

    Article  CAS  PubMed  Google Scholar 

  9. Gubb, D. Genes controlling cellular polarity in Drosophila. Development 1993 Suppl., 269–277 (1993).

  10. Chan, S.D.H. et al. Two homologs of the Drosophila polarity gene frizzled (fz) are widely expressed in mammalian tissues. J Biol Chem. 267, 25202–25207 (1992).

    CAS  PubMed  Google Scholar 

  11. Zhao, Z. et al. A human homologue of the Drosophila polarity gene frizzled has been identified and mapped to 17q21.1. Genomics 27, 370–373 (1995).

    Article  CAS  PubMed  Google Scholar 

  12. Willems, I.E.M.G. et al. Structural alterations in heart valves during left ventricular pressure overload in the rat. Lab Invest. 71, 127–133 (1994).

    CAS  PubMed  Google Scholar 

  13. Wang, Y. et al. A large family of putative transmembrane receptors homologous to the product of the Drosophila tissue polarity gene frizzled. J Biol Chem. 271, 4468–4476 (1996).

    Article  CAS  PubMed  Google Scholar 

  14. Bodmer, R. Heart development in Drosophila and its relationship to vertebrates. Trends Cardiovasc Med. 5, 21–28 (1995).

    Article  CAS  PubMed  Google Scholar 

  15. Wong, L.L. & Adler, P.N. Tissue polarity genes of Drosophila regulate the subcellular location for prehair initiation in pupal wing cells. J Cell Biol. 123, 209–221 (1993).

    Article  CAS  PubMed  Google Scholar 

  16. Eyden, B.P. Brief review of the fibronexus and its significance for myofibroblastic differentiation and tumor diagnosis. Ultrastruct Pathol. 17, 611–622 (1993).

    Article  CAS  PubMed  Google Scholar 

  17. Bhanot, P. et al. A new member of the frizzled family from Drosophila functions as a Wingless receptor. Nature 382, 225–230 (1996).

    Article  CAS  PubMed  Google Scholar 

  18. Krasnow, R.E., Wong, L.L. & Adler, P.N. Dishevelled is a component of the frizzled signaling pathway in Drosophila. Development 121, 4095–4102 (1995).

    CAS  PubMed  Google Scholar 

  19. Pizzuti, A. et al. Human homologue sequences to the Drosophila dishevelled segment-polarity gene are deleted in the DiGeorge syndrome. Am. J. Hum. Genet. 58, 722–729 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Mierop, L.H.S. & Kutsche, L.M. Cardiovascular anomalies in DiGeorge syndrome and importance of neural crest as a possible pathogenetic factor. Am J Cardiol. 58, 133–137 (1986).

    Article  PubMed  Google Scholar 

  21. Passier, R.C.J.J. et al. Activation of angiotensin-converting-enzyme in the infarct zone following myocardial infarction. Am J Physiol. 269, H1268–H1276 (1995).

    CAS  PubMed  Google Scholar 

  22. Dijkstra, C.D. et al. The heterogeneity of mononuclear phagocytes in lymphoid organs: Distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology 54, 589–599 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Blankesteijn, W., Essers-Janssen, Y., Verluyten, M. et al. A homologue of Drosophila tissue polarity gene frizzled is expressed in migrating myofibroblasts in the infarcted rat heart. Nat Med 3, 541–544 (1997). https://doi.org/10.1038/nm0597-541

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm0597-541

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing