Genetic regulatory networks of nephrogenesis: deregulation of WT1 splicing by benzo(a)pyrene

Recent studies have identified AHR as a master regulator of Wilms' tumor suppressor gene (WT1) signaling in the developing kidney. Activation of AHR signaling by environmental chemical is associated with proteasome-mediated degradation of AHR protein, disruption of WT1 alternative splicing, and marked alterations in the regulation of genetic programs of developmental progression in the developing kidney. The complexity of genetic regulatory networks of nephrogenesis controlled by AHR-WT1 interactions will be discussed here with particular emphasis given to the biological and medical consequences that may result from deficits in nephrogenesis that compromise reserve capacity and renal function later in life. Understanding the impact of early-life environmental exposures to chemicals that disrupt AHR signaling can help minimize negative health consequences to pregnant women and their offspring.