The development of the filtration barrier is part of a complex sequence of steps proceeding from the early nephron anlage (renal vesicle) via the comma- and S-shaped body to the capillary loop stage and mature glomerulus. The main players are the podocytes (already in the stage of presumptive podocytes), which hold the commander function in this process, and the endothelial and the mesangial cells. A decisive role is also played by the GBM; its change in composition during the developmental process is a precondition for the final maturation of the podocytes, i.e. for the formation of the foot processes and, clearly subsequent, the slit membrane. Failure in the consecutive developmental stages due to genetic mutations or manipulations leads to characteristic hereditary diseases of increasing severity. The last step in this development, the formation of the slit membrane, marks a caesura between diseases with early and late onset; all disorders without a properly developed slit membrane start prenatally or at birth.
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