Form and function of developing heart valves: coordination by extracellular matrix and growth factor signaling.
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.
Schroeder
Joyce A
JA
Department of Molecular and Cellular Biology, Arizona Cancer Center, University of Arizona, Tucson, USA.
Jackson
Leslie F
LF
Lee
David C
DC
Camenisch
Todd D
TD
D000818:Animals; D004699:Endocardium / Q000196:embryology; D005109:Extracellular Matrix / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006133:Growth Substances / Q000235:genetics / Q000502:physiology*; D006321:Heart / Q000196:embryology; D006351:Heart Valves / Q000196:embryology*; D006801:Humans; D006820:Hyaluronic Acid / Q000502:physiology*; D009024:Morphogenesis; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation
D006133:Growth Substances; D006820:Hyaluronic Acid; D020794:Receptor Protein-Tyrosine Kinases