Nephrin expression and three-dimensional morphogenesis of the Xenopus pronephric glomus
Nephrin expression and three-dimensional morphogenesis of the Xenopus pronephric glomus
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DOI：
10.1002/dvdy.20415
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发表时间：
2005-07-01
影响因子：
2.5
通讯作者：
Vize, PD
中科院分区：
文献类型：
--
作者：
Gerth, VE;Zhou, XL;Vize, PD
Nephrin（NHPS 1）编码约1，200个氨基酸的跨膜蛋白，其在足细胞裂膜形成和功能性哺乳动物肾小球滤过屏障的发育中起关键作用。在具有nephrin基因先天性缺陷的人类和小鼠中，肾小球滤过屏障是有缺陷的，蛋白质渗漏到肾脏滤液中引起危及生命的蛋白尿。这种蛋白质也在果蝇马氏管的星状细胞的形成中起重要作用。在这份报告中，非洲爪蟾nephrin的直系同源物的序列和表达描述使用传统的和新的三维（3D）可视化方法。非洲爪蟾nephrin编码1，238个氨基酸的蛋白质，并在形成的前肾球（相当于哺乳动物肾小球）中高水平表达。表达在阶段25开始，并且特异于前肾球直到至少蝌蚪进食阶段。nephrin表达的双色荧光整装原位分析允许对血管球的3D形状进行成像，并在其整个形态发生过程中与原肾小管形成对比。建立共聚焦数据处理管道，以生成发育中的前肾的体积和表面模型，并使用基于Web的可视化系统来生成形成肾器官的动态和可操作的模型。该系统允许简单的在线形态分析的发展pronephric组件。在鱼类胚胎中，球囊首先横向形成，然后随着原肾成熟向内侧迁移。与斑马鱼不同的是，在非洲爪蟾中，这种迁移在中线处的两个球体完全融合之前停止，但是肾蛋白阳性的球体连接确实在前方形成，并且从阶段38开始连接两个结构。(c)2005 Wiley-Liss，Inc.
Nephrin (NHPS1) encodes a transmembrane protein of approximately 1,200 amino acids that plays a critical role in podocyte slit-diaphragm formation and the development of functional mammalian glomerular filtration barriers. In humans and mice with congenital defects in the nephrin gene, the glomerular filtration barrier is defective and protein leakage into the kidney filtrate causes a life-threatening proteinuria. This protein also plays an essential role in the formation of the stellate cells of the Drosophila Malpighian tubules. In this report, the sequence and expression of a Xenopus ortholog of nephrin is described using both conventional and novel three-dimensional (3D) visualization methodologies. Xenopus nephrin encodes a protein of 1,238 amino acids and is expressed at high levels in the forming pronephric kidney glomus, the equivalent of the mammalian glomerulus. Expression commences at stage 25 and is specific to the pronephric glomus up until at least tadpole feeding stages. Two-color fluorescent whole-mount in situ analysis of nephrin expression allowed the 3D shape of the glomus to be imaged and contrasted to the pronephric tubules throughout its morphogenesis. Confocal data processing pipelines were established to generate both volumetric and surface models of the developing pronephros, and a Web-based visualization system was used to generate dynamic and manipulable models of the forming nephric organs. This system allows simple on-line morphometric analysis of the developing pronephric components. As in fish embryos, the glomera first form laterally then migrate medially as the pronephros matures. Unlike in the zebrafish, in Xenopus, this migration stops short of complete fusion of the two glomera at the midline, but a nephrin-positive glomeral nexus does form anteriorly and links the two structures from stage 38 onward. (c) 2005 Wiley-Liss, Inc.