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

  1. Manjeet K. Rao1,
  2. John Pham1,
  3. J. Saadi Imam1,
  4. James A. MacLean1,
  5. Deepa Murali2,
  6. Yasuhide Furuta2,
  7. Amiya P. Sinha-Hikim3, and
  8. Miles F. Wilkinson1,4
  1. 1Department of Immunology, 2Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA; 3Division of Endocrinology, University of California at Los Angeles School of Medicine, Torrance, California 90502, USA

Abstract

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.

Keywords

Footnotes

  • Supplemental material is available at http://www.genesdev.org.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad1367806.

  • ↵4 Corresponding author. E-MAIL mwilkins{at}mdanderson.org; FAX (713) 563-3357.

    • Accepted November 28, 2005.
    • Received August 23, 2005.
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  1. doi: 10.1101/gad1367806 Genes & Dev. 20: 147-152 Cold Spring Harbor Laboratory Press

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