Heart-valve mesenchyme formation is dependent on hyaluronan-augmented activation of ErbB2-ErbB3 receptors

Todd D Camenisch, Joyce Schroeder, Judy Bradley, Scott E Klewer, John A. McDonald

Research output: Contribution to journalArticle

239 Citations (Scopus)

Abstract

Heart septation and valve malformations constitute the most common anatomical birth defects. These structures arise from the endocardial cushions within the atrioventricular canal (AVC) through dynamic interactions between cushion cells and the extracellular matrix (termed cardiac jelly). Transformation of endothelial cells to mesenchymal cells is essential for the proper development of the AVC and subsequent septation and valve formation. Atrioventricular septal defects can result from incomplete endocardial cushion morphogenesis. We show that hyaluronan-deficient AVC explants from Has2-/- embryos, which normally lack mesenchyme formation, are rescued by heregulin treatment, which restores phosphorylation of ErbB2 and ErbB3. These events were blocked using a soluble ErbB3 molecule, as well as with an inhibitor of ErbB2, herstatin. We show further that ErbB3 is activated during hyaluronan treatment of Has2-/- explants. These data provide a link between extracellular matrix-hyaluronan and ErbB receptor activation during development of early heart-valve and septal mesenchyme.

Original languageEnglish (US)
Pages (from-to)850-855
Number of pages6
JournalNature Medicine
Volume8
Issue number8
DOIs
StatePublished - 2002

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Endocardial Cushions
Heart Valves
Mesoderm
Canals
Hyaluronic Acid
Chemical activation
CD44 Antigens
Neuregulin-1
Morphogenesis
Extracellular Matrix
Defects
Phosphorylation
Embryonic Structures
Endothelial Cells
Endothelial cells
Molecules

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Heart-valve mesenchyme formation is dependent on hyaluronan-augmented activation of ErbB2-ErbB3 receptors. / Camenisch, Todd D; Schroeder, Joyce; Bradley, Judy; Klewer, Scott E; McDonald, John A.

In: Nature Medicine, Vol. 8, No. 8, 2002, p. 850-855.

Research output: Contribution to journalArticle

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