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Form and function of developing heart valves: coordination by extracellular matrix and growth factor signaling

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Abstract

It is becoming clear that converging pathways coordinate early heart valve development and remodeling into functional valve leaflets. The integration of these pathways begins with macro and molecular interactions outside the cell in the extracellular matrix separating the myocardial and endocardial tissue components of the rudimentary heart. Such interactions regulate events at the cell surface through receptors, proteases, and other membrane molecules which in turn transduce signals into the cell. These signals trigger intracellular cascades that transduce cellular responses through both transcription factor and cofactor activation mediating gene induction or suppression. Chamber septation and valve formation occur from these coordinated molecular events within the endocardial cushions to sustain unidirectional blood flow and embryo viability. This review discusses the emerging connection between extracellular matrix and growth factor receptor signaling during endocardial cushion morphogenesis by highlighting the extracellular component, hyaluronan, and erbB receptor functions during early valve development.

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Abbreviations

AV :

Atrioventricular

BMP :

Bone morphogenetic protein

CHD :

Congenital heart defects

ECM :

Extracellular matrix

EGF :

Epidermal growth factor

EGFR :

Epidermal growth factor receptor

EMT :

Epithelial to mesenchymal transformation

ERK :

Extracellular signal regulated kinase

HA :

Hyaluronan

Has :

Hyaluronan synthase

HB :

Heparin-binding

HRG :

Heregulin

HSPG :

Heparan sulfate proteoglycan

MAP :

Mitogen-activated protein

OFT :

Outflow tract

TACE :

Tumor necrosis factor α converting enzyme

TGF :

Transforming growth factor

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Acknowledgements

We appreciate the sharing of unpublished observations by the indicated investigators. We thank Dr. S. Klewer for the type VI collagen images and T. Biazo for graphics support. We thank Drs. J. McDonald and R. Runyan for support. T.D.C. is supported by the American Heart Association and the PANDA Foundation of Arizona.

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Authors and Affiliations

  1. Department of Molecular and Cellular Biology, Arizona Cancer Center, University of Arizona, Tucson, Ariz., USA

    Joyce A. Schroeder

  2. Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina, Chapel Hill, N.C., USA

    Leslie F. Jackson & David C. Lee

  3. Department of Pharmacology and Toxicology, College of Pharmacy, Steele Memorial Children's Research Center, University of Arizona, 1703 E. Mabel St., PO Box 210207, Tucson, AZ 85721-0207, USA

    Todd D. Camenisch

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  1. Joyce A. Schroeder
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  2. Leslie F. Jackson
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  3. David C. Lee
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  4. Todd D. Camenisch
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Correspondence to Todd D. Camenisch.

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Schroeder, J.A., Jackson, L.F., Lee, D.C. et al. Form and function of developing heart valves: coordination by extracellular matrix and growth factor signaling. J Mol Med 81, 392–403 (2003). https://doi.org/10.1007/s00109-003-0456-5

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  • DOI: https://doi.org/10.1007/s00109-003-0456-5

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