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Lookup NU author(s): Dr Ralf KistORCiD
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Heart valve structures derived from mesenchymal cells of the endocardial cushions (ECs) are composed of highly organized cell lineages and extracellular matrix. Sox9 is a transcription factor required for both early and late stages of cartilage formation that is also expressed in the developing valves of the heart. The requirements for Sox9 function during valvulogenesis and adult valve homeostasis in mice were examined by conditional inactivation of Sox9 using Tie2-cre and Col2a1-cre transgenes. Sox9flox/flox;Tie2-cre mice die before E14.5 with hypoplastic ECs, reduced cell proliferation and altered extracellular matrix protein (ECM) deposition. Sox9flox/flox;Col2a1-cre mice die at birth with thickened heart valve leaflets, reduced expression of cartilage-associated proteins and abnormal ECM patterning. Thickened valve leaflets and calcium deposits, characteristic of valve disease, are observed in heterozygous adult Sox9flox/+;Col2a1-cre mice. Therefore, Sox9 is required early in valve development for expansion of the precursor cell population and later is required for normal expression and distribution of valvular ECM proteins. These data indicate that Sox9 is required for early and late stages of valvulogenesis and identify a potential role for Sox9 in valve disease mechanisms. © 2007 Elsevier Inc. All rights reserved.
Author(s): Lincoln J, Kist R, Scherer G, Yutzey KE
Publication type: Article
Publication status: Published
Journal: Developmental Biology
ISSN (print): 0012-1606
ISSN (electronic): 1095-564X
Publisher: Academic Press
PubMed id: 17350610
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