Tissue-specific RNAi reveals that WT1 expression in nurse cells controls germ cell survival and spermatogenesis

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Tissue-specific RNAi reveals that WT1 expression in nurse cells controls germ cell survival and spermatogenesis
November 28, 2005
Manjeet K. Rao, John Pham, J. Saadi Imam, James A. MacLean, Deepa Murali, Yasuhide Furuta, Amiya P. Sinha-Hikim and Miles F. Wilkinson
Genes & Development
Using a novel tissue-specific RNA interference (RNAi) approach that mimics the principle by which naturally occurring microRNAs (miRNA) are made, we demonstrate that the Wilms' tumor 1 (WT1) transcription factor has an essential role in spermatogenesis. Mice depleted of WT1 in Sertoli nurse cells suffered from increased germ cell apoptosis, loss of adherens junctions, disregulation of adherence junction-associated genes, and impaired fertility. These effects were recapitulated in transgenic mice expressing a dominant-negative form of WT1 in Sertoli cells, demonstrating the validity of our RNAi approach. Our results indicate that the tumor suppressor WT1 promotes Sertoli cell-germ cell signaling events driving spermatogenesis.
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