Mahtab Edris A F, Vicente-Steijn Rebecca, Hahurij Nathan D, Jongbloed Monique R M, Wisse Lambertus J, DeRuiter Marco C, Uhrin Pavel, Zaujec Jan, Binder Bernd R, Schalij Martin J, Poelmann Robert E, Gittenberger-de Groot Adriana C
Department of Anatomy and Embryology, Leiden University Medical Center, The Netherlands.
Dev Dyn. 2009 Jan;238(1):183-93. doi: 10.1002/dvdy.21819.
We investigated the role of podoplanin in development of the sinus venosus myocardium comprising the sinoatrial node, dorsal atrial wall, and primary atrial septum as well as the myocardium of the cardinal and pulmonary veins. We analyzed podoplanin wild-type and knockout mouse embryos between embryonic day 9.5-15.5 using immunohistochemical marker podoplanin; sinoatrial-node marker HCN4; myocardial markers MLC-2a, Nkx2.5, as well as Cx43; coelomic marker WT-1; and epithelial-to-mesenchymal transformation markers E-cadherin and RhoA. Three-dimensional reconstructions were made and myocardial morphometry was performed. Podoplanin mutants showed hypoplasia of the sinoatrial node, primary atrial septum, and dorsal atrial wall. Myocardium lining the wall of the cardinal and pulmonary veins was thin and perforated. Impaired myocardial formation is correlated with abnormal epithelial-to-mesenchymal transformation of the coelomic epithelium due to up-regulated E-cadherin and down-regulated RhoA, which are controlled by podoplanin. Our results demonstrate an important role for podoplanin in development of sinus venosus myocardium.
我们研究了血小板反应蛋白-1在由窦房结、心房背壁和原始房间隔组成的静脉窦心肌以及主静脉和肺静脉心肌发育中的作用。我们使用免疫组织化学标记物血小板反应蛋白-1、窦房结标记物HCN4、心肌标记物MLC-2a、Nkx2.5以及Cx43、体腔标记物WT-1和上皮-间质转化标记物E-钙黏蛋白和RhoA，分析了胚胎第9.5 - 15.5天的血小板反应蛋白-1野生型和基因敲除小鼠胚胎。进行了三维重建并进行了心肌形态测量。血小板反应蛋白-1突变体表现出窦房结、原始房间隔和心房背壁发育不全。主静脉和肺静脉壁内衬的心肌变薄且有穿孔。心肌形成受损与体腔上皮因E-钙黏蛋白上调和RhoA下调而发生的异常上皮-间质转化相关，而这两者均受血小板反应蛋白-1调控。我们的结果证明了血小板反应蛋白-1在静脉窦心肌发育中的重要作用。
