Ureter development and associated congenital anomalies

Malformations of the ureter are among the most common birth defects in humans. Although some of these anomalies are asymptomatic, others are clinically relevant, causing perinatal lethality or progressing to kidney failure in childhood. The genetic causes and developmental aetiology of ureteral anomalies are difficult to study in humans; however, embryological and genetic analyses in the mouse have provided insights into the complex developmental programmes that govern ureter formation from simple tissue primordia, and the pathological consequences that result from disruption of these programmes. Abnormalities in the formation of the nephric duct and ureteric bud lead to changes in the number of ureters (and kidneys), whereas the formation of ectopic ureteric buds, failure of the nephric duct to target the cloaca or failure of the distal ureter to mature underlie vesicoureteral reflux, ureter ectopia, ureterocoele and subsequent hydroureter. Alterations in ureter specification, early growth or cyto-differentiation programmes have now also been associated with various forms of perinatal hydroureter and hydronephrosis as a consequence of functional obstruction. The characterization of cellular processes and molecular drivers of ureterogenesis in the mouse may not only aid understanding of the aetiology of human ureteral anomalies, improve prognostication and benefit the development of therapeutic strategies, but may also prove important for efforts to generate a bioartificial organ.