Precocious expression of the Wilms' tumor gene xWT1 inhibits embryonic kidney development in Xenopus laevis

The tumor suppressor WT1 has been demonstrated to have a wide variety of activities in vitro and is required for metanephric development in vivo. In the experiments presented here, the Xenopus pronephros was used as a simple model system to examine the activity of Xenopus WT1 (xWT1) during kidney development. xWT1 was ectopically expressed in Xenopus embryos by mRNA injection and found to inhibit pronephric tubule development. Confocal microscopy confirmed this observation and revealed that the inhibition was the result of a failure to form a pronephric anlage of appropriate size rather than a defect in epithelialization. Examination of Xlim-1 expression, an early molecular marker of pronephric specification, in tailbud embryos indicated that injected xWT1 mRNA inhibited pronephric specification prior to any overt sign of morphogenesis (Xenogus stage 21). These results suggest that xWT1 may act to repress tubule-specific gene expression in the portion of the pronephros fated to fern; its vascular structure, the glomus. (C) 1998 Academic Press.