Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
J Histochem Cytochem. 2013 Apr;61(4):313-24. doi: 10.1369/0022155413477115. Epub 2013 Jan 15.
Slit diaphragm (SD) is a highly specialized intercellular junction between podocyte foot processes and plays a crucial role in the formation of the filtration barrier. In this study, we examined the developmental localization of Nephrin, an essential component of SD, in the pronephric glomerulus of zebrafish and medaka. In the mature glomerulus of both fish, Nephrin is localized along the glomerular basement membrane as seen in mammals, indicating that Nephrin is localized at the SD. Interestingly, Nephrin was detected already in immature podocytes before the SD and foot processes started to form in both fish. Nephrin was localized along the cell surface of immature podocytes but as different localization patterns. In zebrafish, Nephrin signal bordered the lateral membrane of podocytes, which were columnar in shape, as in rat immature podocytes. However, in medaka immature podocytes, Nephrin was localized in a punctate pattern among podocyte cell bodies. These findings suggest that Nephrin needs to be integrated to the membrane before the formation of the SD and then moves to the proper site to form the SD. Furthermore, a podocyte-specific marker, such as Nephrin, should be a useful tool for the future analysis of pronephric glomerular development in fish mutants and morphants.
裂孔隔膜(SD)是足细胞足突之间的一种高度特化的细胞间连接,在滤过屏障的形成中起着至关重要的作用。在这项研究中,我们研究了 Nephrin 在斑马鱼和日本青鳉的肾前肾小球中的发育定位。在这两种鱼类的成熟肾小球中,Nephrin 沿着肾小球基底膜定位,就像在哺乳动物中一样,这表明 Nephrin 定位于 SD。有趣的是,在 SD 和足突开始形成之前,在两种鱼类的未成熟足细胞中已经检测到 Nephrin。Nephrin 沿着未成熟足细胞的细胞表面定位,但存在不同的定位模式。在斑马鱼中,Nephrin 信号沿着足细胞的侧膜定位,足细胞呈柱状,类似于大鼠未成熟的足细胞。然而,在日本青鳉的未成熟足细胞中,Nephrin 呈点状定位于足细胞体之间。这些发现表明,Nephrin 需要在 SD 形成之前整合到膜上,然后移动到适当的位置形成 SD。此外,像 Nephrin 这样的足细胞特异性标记物应该是未来分析鱼类突变体和形态发生体的肾前肾小球发育的有用工具。