Pod1/Tcf21 is regulated by retinoic acid signaling and inhibits differentiation of epicardium-derived cells into smooth muscle in the developing heart
详细信息 查看全文
- 作者：Caitlin M. Braitsch ; Michelle D. Combs ; Susan E. Quaggin ; Katherine E. Yutzey
- 关键词：Heart development ; EPDC ; Pod1 ; Tcf21 ; Chicken ; Mouse
- 刊名：Developmental Biology
- 出版年：2012
- 出版时间：15 August, 2012
- 年：2012
- 卷：368
- 期：2
- 页码：345-357
- 全文大小：2841 K
文摘
Epicardium-derived cells (EPDCs) invade the myocardium and differentiate into fibroblasts and vascular smooth muscle (SM) cells, which support the coronary vessels. The transcription factor Pod1 (Tcf21) is expressed in subpopulations of the epicardium and EPDCs in chicken and mouse embryonic hearts, and the transcription factors WT1, NFATC1, and Tbx18 are expressed in overlapping and distinct subsets of Pod1-expressing cells. Expression of <em>Pod1em> and <em>WT1em>, but not <em>Tbx18em> or <em>NFATC1em>, is activated with all-<em>transem>-retinoic acid (RA) treatment of isolated chick EPDCs in culture. In intact chicken hearts, RA inhibition leads to decreased Pod1 expression while RA treatment inhibits SM differentiation. The requirements for Pod1 in differentiation of EPDCs in the developing heart were examined in mice lacking Pod1. Loss of Pod1 in mice leads to epicardial blistering, increased SM differentiation on the surface of the heart, and a paucity of interstitial fibroblasts, with neonatal lethality. Epicardial epithelial-to-mesenchymal transition (EMT) and endothelial differentiation of coronary vessels are relatively unaffected. On the surface of the myocardium, expression of multiple SM markers is increased in Pod1-deficient EPDCs, demonstrating premature SM differentiation. Increased SM differentiation also is observed in Pod1-deficient lung mesenchyme. Together, these data demonstrate a critical role for Pod1 in controlling mesenchymal progenitor cell differentiation into SM and fibroblast lineages during cardiac development.