Transcriptional regulation of heart valve progenitor cells.
The development and normal function of the heart valves requires complex interactions among signaling molecules, transcription factors and structural proteins that are tightly regulated in time and space. Here we review the roles of critical transcription factors that are required for specific aspects of normal valve development. The early progenitors of the heart valves are localized in endocardial cushions that express transcription factors characteristic of mesenchyme, including Twist1, Tbx20, Msx1 and Msx2. As the valve leaflets mature, they are composed of complex stratified extracellular matrix proteins that are regulated by the transcriptional functions of NFATc1, Sox9, and Scleraxis. Each of these factors has analogous functions in differentiation of related connective tissue lineages. Together, the precise timing and localized functions of specific transcription factors control cell proliferation, differentiation, elongation, and remodeling processes that are necessary for normal valve structure and function. In addition, there is increasing evidence that these same transcription factors contribute to congenital, as well as degenerative, valve disease.
Chakraborty
Santanu
S
Division of Molecular Cardiovascular Biology, Cincinnati Children's Medical Center, ML 7020, 240 Albert Sabin Way, Cincinnati, OH 45229, USA.
Combs
Michelle D
MD
Yutzey
Katherine E
KE
D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D004699:Endocardium / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006351:Heart Valves / Q000196:embryology* / Q000254:growth & development; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D051957:MSX1 Transcription Factor / Q000235:genetics; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D055758:SOX9 Transcription Factor / Q000235:genetics; D015398:Signal Transduction; D013234:Stem Cells; D020825:T-Box Domain Proteins / Q000235:genetics; D014158:Transcription, Genetic; D051879:Twist-Related Protein 1 / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D055758:SOX9 Transcription Factor; D020825:T-Box Domain Proteins; D051879:Twist-Related Protein 1; C484083:MSX1 protein, human; C084119:MSX2 protein; C494003:NFATC1 protein, human; C093504:SCX protein, human; C527932:SOX9 protein, human; C420984:TBX20 protein, human; C103173:TWIST1 protein, human