Differentiation of epithelial foot processes and filtration slits: sequential appearance of occluding junctions, epithelial polyanion, and slit membranes in developing glomeruli.
Differentiation of epithelial foot processes and filtration slits: sequential appearance of occluding junctions, epithelial polyanion, and slit membranes in developing glomeruli.
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上皮足突和滤过缝的分化：发育中的肾小球中闭塞连接、上皮聚阴离子和缝膜的顺序出现。
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发表时间：
1978
期刊：
影响因子：
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通讯作者：
M. Farquhar
中科院分区：
文献类型：
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作者：
W. Reeves;J. Caulfield;M. Farquhar
检查新生大鼠未成熟肾小球的内脏肾小球上皮，以确定足突和滤过缝分化过程中发生的事件顺序。定义了肾小球发育的四个不同阶段：囊泡、S形体、发育中的毛细血管袢和成熟阶段。在囊泡阶段，肾小球和肾小管上皮的前体细胞通过其顶端的闭塞连接而连接起来。在S形身体阶段，管状和壁层内脏肾小球上皮分化，闭塞小带分别沿着假定的小管腔和鲍曼空间保留。随着毛细血管袢的出现，壁层和管状连接保持这种排列，但内脏上皮的连接在沿着侧细胞边缘的不同水平上可见，表明它们沿着侧细胞表面从顶端迁移到基部。最初，广泛的上皮过程覆盖发育中的基底膜的整个外部。交界迁移后，可以看到上皮突起相互交叉，并且这些突起通过局灶性闭塞连接（黄斑或筋膜）连接起来。随着更复杂的叉指，越来越少的细胞间空间被闭塞连接所封闭，连接变得越来越不广泛，并且具有由缝隙膜桥接的足突的正常缝隙结构占主导地位。胶体铁染色（即上皮聚阴离子）首先在毛细血管袢阶段早期沿侧上皮细胞表面检测到，并在发生叉指的同时沿面向基底膜的基底细胞表面集中。因此，在发生叉指的同时，面向基底膜。因此，唾液蛋白在足突和缝隙发育之前就出现在上皮细胞表面。这一发现与正常足突和缝隙组织的发育和维持可能需要上皮聚阴离子的假设一致。在广泛叉指发展之前，分化的肾小球上皮与肾病上皮有许多惊人的相似之处：足突宽，数量减少，并且经常由局灶性闭塞连接连接；狭缝隔膜数量减少并远离基底膜；过滤缝中出现梯状结构。因此，在氨基核苷肾病中观察到的上皮变化似乎代表了更原始组织的“去分化”，并且该疾病过程早期发生的事件代表了正常肾小球发育过程中发生的事件的逆向再现。
The visceral glomerular epithelium of immature glomeruli from newborn rats was examined in order to determine the sequence of events that occurs during differentiation of foot processes and filtration slits. Four different stages of glomerular development were defined: vesicle, S-shaped body, developing capillary loop, and maturing stages. During the vesicle stage, the precursor cells of the glomerular and tubular epithelium are joined by occluding junctions at their apices. During the S-shaped body stage, the tubular and parietal visceral glomerular epithelium differentiate, and the occluding zonulae remain along the presumptive tubule lumen and Bowman's space, respectively. With the appearance of capillary loops the parietal and tubular junctions maintain this arrangement, but the junctions of the visceral epithelium are seen at various levels along the lateral cell margins, suggesting that they migrate along the lateral cell surfaces from apex to base. Initially, broad epithelial processes cover the entire outer aspect of the developing basement membrane. After junctional migration interdigitation of epithelial processes is seen, and the processes are joined by focal occluding junctions (maculae or fasciae). With more elaborate interdigitation, fewer and fewer intercellular spaces are closed by occluding junctions, the junctions become less and less extensive, and normal slit architecture with foot processes bridged by slit membranes predominate. Colloidal iron staining (i.e., epithelial polyanion) is first detected along the lateral epithelial cell surfaces early in the capillary loop stage and becomes concentrated along their basal cell surfaces facing the basement membrane at about the same time as interdigitation is occurring. Therefore, facing the basement membrane at about the same time as interdigitation is occurring. Therefore, sialoproteins appear on the epithelial cell surfaces prior to the development of foot processes and slits. This finding is in keeping with the assumption that epithelial polyanion may be required for development and maintenance of normal foot process and slit organization. Prior to the development of extensive interdigitation, the differentiating glomerular epithelium bears a number of striking similarities to the nephrotic epithelium: foot processes are broad, reduced in number, and often joined by focal occluding junctions; slit diaphragms are reduced in number and displaced away from the basement membrane; and ladder-like structures occur in the filtration slits. The epithelial changes seen in aminonucleoside nephrosis therefore appear to represent a "dedifferentiation" to a more primitive organization, and the events that occur early in this disease process represent a rerun inreverse of events that occur during normal glomerular development.