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

Manjeet K. Rao, John Pham, J. Saadi Imam, James A. MacLean, Deepa Murali, Yasuhide Furuta, Amiya P. Sinha-Hikim, Miles F. Wilkinson

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)147-152
Number of pages6
JournalGenes and Development
Volume20
Issue number2
DOIs
StatePublished - Jan 15 2006

Keywords

  • Germ cell
  • RNAi
  • Sertoli cell
  • Spermatogenesis
  • WT1
  • miRNA

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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