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

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.

• Authors: Manjeet K Rao, John Pham, J Saadi Imam, James A MacLean, Deepa Murali, Yasuhide Furuta, Amiya P Sinha-Hikim, Miles F Wilkinson
• Journal: Genes & development (Genes Dev) Vol. 20 Issue 2 Pg. 147-52 (Jan 15 2006) ISSN: 0890-9369 [Print] United States
• PMID: 16418481 (Publication Type: Journal Article)

Chemical References

• RNA Precursors
• Transcription Factors
• WT1 Proteins
• DNA Polymerase II
• DROSHA protein, human
• Ribonuclease III

Topics

• Adherens Junctions (metabolism)
• Animals
• Apoptosis (genetics)
• Cell Survival (genetics)
• DNA Polymerase II (genetics, metabolism)
• Gene Expression
• Germ Cells (enzymology, physiology)
• Gonads (enzymology, metabolism)
• Male
• Mice
• Mice, Transgenic
• Mutation
• Organ Specificity
• RNA Interference
• RNA Precursors (metabolism)
• Reproducibility of Results
• Ribonuclease III (metabolism)
• Sertoli Cells (metabolism)
• Spermatogenesis (genetics, physiology)
• Transcription Factors (genetics, metabolism)
• Transfection
• WT1 Proteins (genetics, metabolism)