Wnt5a Is Necessary for Normal Kidney Development in Zebrafish and Mice

Abstract

<b><i>Background:</i></b> Wnt5a is important for the development of various organs and postnatal cellular function. Little is known, however, about the role of <i>Wnt5a</i> in kidney development, although <i>WNT5A</i> mutations were identified in patients with Robinow syndrome, a genetic disease which includes developmental defects in kidneys. Our goal in this study was to determine the role of <i>Wnt5a</i> in kidney development. <b><i>Methods:</i></b> Whole-mount in situ hybridization was used to establish the expression pattern of <i>Wnt5a</i> during kidney development. Zebrafish with <i>wnt5a</i> knockdown and <i>Wnt5a</i> global knockout mice were used to identify kidney phenotypes. <b><i>Results:</i></b> In zebrafish, <i>wnt5a</i> knockdown resulted in glomerular cyst formation and dilated renal tubules. In mice, <i>Wnt5a</i> global knockout resulted in pleiotropic, but severe, kidney phenotypes, including agenesis, fused kidney, hydronephrosis and duplex kidney/ureter. <b><i>Conclusions:</i></b> Our data demonstrated the important role of <i>Wnt5a</i> in kidney development. Disrupted Wnt5a resulted in kidney cysts in zebrafish and pleiotropic abnormal kidney development in mice.