Sox9 is required for precursor cell expansion and extracellular matrix organization during mouse heart valve development. Dev Biol 2007 May 01;305(1):120-32
Date
03/14/2007Pubmed ID
17350610Pubmed Central ID
PMC1920559DOI
10.1016/j.ydbio.2007.02.002Scopus ID
2-s2.0-34247249338 (requires institutional sign-in at Scopus site) 152 CitationsAbstract
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. Sox9(flox/flox);Tie2-cre mice die before E14.5 with hypoplastic ECs, reduced cell proliferation and altered extracellular matrix protein (ECM) deposition. Sox9(flox/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 Sox9(flox/+);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.
Author List
Lincoln J, Kist R, Scherer G, Yutzey KEAuthor
Joy Lincoln PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Differentiation
Extracellular Matrix Proteins
Gene Expression Regulation, Developmental
Gene Silencing
Heart Valves
High Mobility Group Proteins
Immunohistochemistry
Mice
SOX9 Transcription Factor
Transcription Factors
Transgenes