The Wilms tumor suppressor gene WT1, which is mutated in 10-15% of Wilms tumor -- a pediatric kidney cancer -- encodes a transcription factor with C2H2 zinc finger DNA binding domain. WT1 is proposed to regulate transcription of genes that are critical for the initiation and differentiation of kidney, gonad, spleen, and adrenal gland since wt1-null mouse embryos lack all of these organs. In addition to Wilms tumor, other human syndromes and diseases are also caused by mutations in the WT1 gene such as Danys-Drash and Frasier syndromes. Using microarray expression profiling, we have identified a number of WT1 target genes that appears to be important for kidney development. The target genes were independently verified using quantitative RT-PCR, chromatin-immunoprecipitation, promoter-reporter assay and expression in WT1-positive cells in the develping kidneys. To examine the physiological role of these targets during kidney development, we used in vitro kidney organ culture assay to determine their effects on kidney differentiation. Identification of the target genes and defining their role during development will provide further insights to the development of Wilms tumor and organogenesis in general.
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