FIGURE 20.9 • Scanning electron micrograph of the interior surface of a glomerular capillary. The wall of the capillary shows horizontal ridges formed by the cytoplasm of the endothelial cell. Elsewhere, fenestrations are seen as numerous dark oval and circular profiles. 5,600. (Courtesy of Dr. C. Craig Tisher.)  Visceral layer of Bowman’s capsule, which contains specialized cells called podocytes or visceral epithelial cells. These cells extend processes around the glomerular capillaries (Fig. 20.11 and Plate 76, page 732). The podocytes arise during embryonic development from one of the blind ends of the developing nephron through  invagination of the end of the tubule to form a double-layered epithelial cup. The inner cell layer (i.e., the visceral cell layer) lies in  apposition to a capillary network, the glomerulus, which forms at this site. The outer layer of these cells, the parietal layer, forms the squamous cells of Bowman’s capsule. The cup eventually closes to form the spherical structure containing the glomerulus. As they differentiate, the podocytes extend processes around the capillaries and develop numerous secondary processes called pedicels or foot processes. The foot processes interdigitate with foot processes of neighboring podocytes, a feature that can be clearly seen with the scanning electron microscope (SEM; Fig. 20.12). The elongated spaces between the interdigitating foot  processes, called fltration slits, are about 40 nm wide and covered by an ultrathin fltration slit diaphragm that spans the filtration slit slightly above the GBM (Fig. 20.13, inset).
Nephrin is an important structural protein of the filtration slit diaphragm.
Recent studies of the fltration slit diaphragm revealed its complex protein structure as a zipper-like sheet configuration with a central density. A transmembrane protein, nephrin is
FIGURE 20.10 • Immunofuorescent-stained glomerular basement membrane in human kidney. Glomerular basement membrane (GBM) is composed of five (1 to 5) of the six chains of type IV collagen. This high magnification micrograph of the GBM within the kidney glomerulus was obtained using primary monoclonal antibodies against 1 chain of type IV collagen molecules that were visualized by secondary antibody conjugated with fluorescein dye. 1,200. (Courtesy of Dr. L. Barisoni.) a key structural and functional component of the slit diaphragm. Nephrin molecules emerging from opposite foot processes interact in the center of the slit (homophilic interactions), forming a central density with pores on both sides (Fig. 20.14). This intercellular protein sheet also contains other adhesion molecules, such as Neph-1, Neph-2, P-cadherin, FAT1, and FAT 2. The filtration slit diaphragm is firmly anchored to numerous actin filaments within the foot processes of podocytes. Regulation and maintenance of the actin cytoskeleton of podocytes has emerged as a critical process for regulating size, patency, and selectivity of the filtration slits. Mutations in the nephrin gene (NPHS1) are associated with congenital nephrotic syndrome, a disease characterized by massive proteinuria and edema.
Endothelial surface layer of glomerular capillaries and subpodocyte space also make an important contribution to overall glomerular function.