Scleraxis is required for cell lineage differentiation and extracellular matrix remodeling during murine heart valve formation in vivo. Circ Res 2008 Oct 24;103(9):948-56
Date
09/20/2008Pubmed ID
18802027Pubmed Central ID
PMC2743952DOI
10.1161/CIRCRESAHA.108.177238Scopus ID
2-s2.0-55449128620 (requires institutional sign-in at Scopus site) 97 CitationsAbstract
Heart valve structures, derived from mesenchyme precursor cells, are composed of differentiated cell types and extracellular matrix arranged to facilitate valve function. Scleraxis (scx) is a transcription factor required for tendon cell differentiation and matrix organization. This study identified high levels of scx expression in remodeling heart valve structures at embryonic day 15.5 through postnatal stages using scx-GFP reporter mice and determined the in vivo function using mice null for scx. Scx(-/-) mice display significantly thickened heart valve structures from embryonic day 17.5, and valves from mutant mice show alterations in valve precursor cell differentiation and matrix organization. This is indicated by decreased expression of the tendon-related collagen type XIV, increased expression of cartilage-associated genes including sox9, as well as persistent expression of mesenchyme cell markers including msx1 and snai1. In addition, ultrastructure analysis reveals disarray of extracellular matrix and collagen fiber organization within the valve leaflet. Thickened valve structures and increased expression of matrix remodeling genes characteristic of human heart valve disease are observed in juvenile scx(-/-) mice. In addition, excessive collagen deposition in annular structures within the atrioventricular junction is observed. Collectively, our studies have identified an in vivo requirement for scx during valvulogenesis and demonstrate its role in cell lineage differentiation and matrix distribution in remodeling valve structures.
Author List
Levay AK, Peacock JD, Lu Y, Koch M, Hinton RB Jr, Kadler KE, Lincoln JAuthor
Joy Lincoln PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AgingAnimals
Basic Helix-Loop-Helix Transcription Factors
Cartilage
Cell Differentiation
Cell Lineage
Collagen
Extracellular Matrix
Fibrosis
Gene Expression Regulation, Developmental
Gestational Age
Glycoproteins
Green Fluorescent Proteins
Heart Valve Diseases
Heart Valves
Mesoderm
Mice
Mice, Knockout
Organogenesis
Recombinant Proteins