DIFFERENTIATION OF EPITHELIAL FOOT PROCESSES AND FILTRATION SLITS - SEQUENTIAL APPEARANCE OF OCCLUDING JUNCTIONS, EPITHELIAL POLYANION, AND SLIT MEMBRANES IN DEVELOPING GLOMERULI

Abstract

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 were 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 were seen at various levels along the lateral cell margins, suggesting that they migrated 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 was seen and the processes were joined by focal occluding junctions (maculae or fasciae). With more elaborate interdigitation, fewer and fewer intercellular spaces were closed by occluding junctions, the junctions became less and less extensive, and normal slit architecture with foot processes bridged by slit membranes predominate. Colloidal iron staining (i.e., epithelial polyanion) was 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, sialoproteins appear on the epithelial cell surfaces prior to the development of foot processes and slits. 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 were broad, reduced in number and often joined by focal occluding junctions; slit diaphragms were reduced in number and displaced away from the basement membrane; and ladder-like structures occur red 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 in reverse of events that occur during normal glomerular development.