Renal Development and Molecular Pathogenesis of Renal Dysplasia

Abstract Renal dysplasia is a leading cause of chronic kidney disease and end stage kidney disease in children. Understanding the molecular pathogenesis of renal maldevelopment began in the 1950s with classical studies by Clifford Grobstein, who isolated and characterized primordial tissues that interact to form the metanephric (adult) kidney. Since then, studies have shown that the following four embryonic tissues develop and send reciprocal signaling to form the kidney: the nephrogenic mesenchyme, the ureteric bud, the stromal mesenchyme, and the renal vasculature. Molecular biology and gene targeting techniques have also identified many genes and signaling pathways required for proper kidney formation in animal models. Recently epigenetic mechanisms have also been described as necessary for renal development in animal models. Studies in patients with syndromic and nonsyndromic renal dysplasia and other congenital renal malformations have identified many causative genetic defects that were previously identified in animal models. This chapter first reviews the molecular control of the embryonic tissues that form the kidney and then discusses the genes known to contribute to renal dysplasia in patients.