Epicardial derived cell epithelial to mesenchymal transition and fate specification require PDGF receptor signaling
| Autor: | Michelle D. Tallquist, Caroline Y. Sung, Christopher L. Smith, Seung Tae Baek |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Epithelial-Mesenchymal Transition
Receptor Platelet-Derived Growth Factor alpha Physiology medicine.medical_treatment Receptor expression Cell Mice Transgenic SOX9 Article Receptor Platelet-Derived Growth Factor beta Mice medicine Animals Epithelial–mesenchymal transition biology Heart development Growth factor Gene Expression Regulation Developmental SOX9 Transcription Factor Sex-Determining Region Y Protein medicine.anatomical_structure biology.protein Cancer research Signal transduction Cardiology and Cardiovascular Medicine Pericardium Platelet-derived growth factor receptor Signal Transduction |
| Popis: | Rationale: 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. Methods and 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. |
| Databáze: | OpenAIRE |
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