title: Epicardial-derived cell epithelial-to-mesenchymal transition and fate specification require PDGF receptor signaling.
abstract: BACKGROUND
  In early heart development, platelet-derived growth factor (PDGF) receptor expression in the heart ventricles is restricted to the epicardium. Previously, we showed that PDGFRβ is required for coronary vascular smooth muscle cell (cVSMC) development, but a role for PDGFRα has not been identified. Therefore, we investigated the combined and independent roles of these receptors in epicardial development.
  
  
  OBJECTIVE
  To understand the contribution of PDGF receptors in epicardial development and epicardial-derived cell fate determination.
  
  
  RESULTS
  By generating mice with epicardial-specific deletion of the PDGF receptors, we found that epicardial epithelial-to-mesenchymal transition (EMT) was defective. Sox9, an SRY-related transcription factor, was reduced in PDGF receptor-deficient epicardial cells, and overexpression of Sox9 restored epicardial migration, actin reorganization, and EMT gene expression profiles. The failure of epicardial EMT resulted in hearts that lacked epicardial-derived cardiac fibroblasts and cVSMC. Loss of PDGFRα resulted in a specific disruption of cardiac fibroblast development, whereas cVSMC development was unperturbed.
  
  
  CONCLUSIONS
  Signaling through both PDGF receptors is necessary for epicardial EMT and formation of epicardial-mesenchymal derivatives. PDGF receptors also have independent functions in the development of specific epicardial-derived cell fates.
authors.affiliation: Department of Molecular Biology, MC9148, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Smith
authors.forename: Seung Tae
authors.initials: ST
authors.lastname: Baek
authors.forename: Caroline Y
authors.initials: CY
authors.lastname: Sung
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Tallquist
mesh_terms: D000818:Animals; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D010496:Pericardium / Q000166:cytology / Q000196:embryology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051876:Sex-Determining Region Y Protein / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D055758:SOX9 Transcription Factor; D051876:Sex-Determining Region Y Protein; C527933:Sox9 protein, mouse; C497746:Sry protein, mouse; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta