Podocyte Differentiation and Glomerulogenesis

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Abstract
Our understanding of the morphologic features of glomerular assembly, and indeed of the development of the nephron and the entire kidney, owe much to the work of Edith Potter and her colleague Vitoon Osathanondh during the mid 1960s. In a seminal series of articles that are today overly neglected, they provided much of understanding of how the kidney as an entire organ is assembled (5–10). With regard to the glomerulus, it was shown how it emerges from one end of the S-shaped body during the development of the nephron (10). In understanding this process, and indeed understanding the development of the nephron in its entirety, it is essential to convert two-dimensional pictures into a three-dimensional understanding. This is especially difficult as the nephron is not a fully symmetrical structure on all axes. With these caveats in mind, the following is a description of glomerular development. As shown in Figures 1A and 1B, at one end of the S-shaped body a layer of columnar epithelial cells is present, which represents the future visceral epithelial cells or podocytes. The basal aspect of these cells rests on the future glomerular basement membrane (GBM); on the other side of this basement membrane is a cleft between the podocytes and the cells, which will contribute to the tubular portion of the nephron. The cells that will contribute to the glomerular capillaries, i.e., endothelial and mesangial cells, migrate into this cleft. The origin of these cells is a subject of ongoing research and, as mentioned above, has been discussed in recent reviews (1–4). On the other side of this patch of future podocytes, overlying their apical surface, is a lining of thin cells that will become the parietal epithelium, also known as Bowman’s capsule.