Kuechlin Sebastian, Schoels Maximilian, Slanchev Krasimir, Lassmann Silke, Walz Gerd, Yakulov Toma A
Renal Division, Department of Medicine, University Freiburg Medical Center, Hugstetter Str. 55, 79106 Freiburg, Germany.
Institute of Surgical Pathology, Medical Center and Faculty of Medicine - University of Freiburg, Breisacherstr. 115A, 79106, Freiburg, Germany; Center for Biological Signaling Studies (BIOSS), Albertstr. 19, 79104 Freiburg, Germany.
Biochem Biophys Res Commun. 2017 May 27;487(2):209-215. doi: 10.1016/j.bbrc.2017.04.035. Epub 2017 Apr 12.
Epithelial cell adhesion molecule EpCAM is a transmembrane glycoprotein that is dynamically expressed in human and murine renal epithelia during development. The levels of EpCAM in the renal epithelium are upregulated both during regeneration after ischemia/reperfusion injury and in renal-derived carcinomas. The role of EpCAM in early kidney development, however, has remained unclear. The zebrafish pronephros shows a similar segmentation pattern to the mammalian metanephric nephron, and has recently emerged as a tractable model to study the regulatory programs governing early nephrogenesis. Since EpCAM shows persistent expression in the pronephros throughout early development, we developed a method to study the global changes in gene expression in specific pronephric segments of wild type and EpCAM-deficient zebrafish embryos. In epcam mutants, we found 379 differentially expressed genes. Gene ontology analysis revealed that EpCAM controls various developmental programs, including uretric bud development, morphogenesis of branching epithelium, regulation of cell differentiation and cilium morphogenesis.
上皮细胞粘附分子EpCAM是一种跨膜糖蛋白,在发育过程中在人和小鼠肾上皮中动态表达。肾上皮中EpCAM的水平在缺血/再灌注损伤后的再生过程以及肾源性癌中均上调。然而,EpCAM在肾脏早期发育中的作用仍不清楚。斑马鱼前肾显示出与哺乳动物后肾肾单位相似的节段模式,并且最近已成为研究控制早期肾发生的调控程序的易处理模型。由于EpCAM在整个早期发育过程中在前肾中持续表达,我们开发了一种方法来研究野生型和EpCAM缺陷型斑马鱼胚胎特定前肾节段中基因表达的全局变化。在epcam突变体中,我们发现了379个差异表达基因。基因本体分析表明,EpCAM控制各种发育程序,包括输尿管芽发育、分支上皮的形态发生、细胞分化调节和纤毛形态发生。