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

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 cel...

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Bibliographic Details
Published in:Genes & development 2006-01, Vol.20 (2), p.147-152
Main Authors: Rao, Manjeet K, Pham, John, Imam, J Saadi, MacLean, James A, Murali, Deepa, Furuta, Yasuhide, Sinha-Hikim, Amiya P, Wilkinson, Miles F
Format: Article
Language:English
Subjects:
Adherens Junctions - metabolism
Animals
Apoptosis - genetics
Cell Survival - genetics
DNA Polymerase II - genetics
DNA Polymerase II - metabolism
Gene Expression
Germ Cells - enzymology
Germ Cells - physiology
Gonads - enzymology
Gonads - metabolism
Male
Mice
Mice, Transgenic
Mutation
Organ Specificity
Reproducibility of Results
Research Communications
Ribonuclease III - metabolism
RNA Interference
RNA Precursors - metabolism
Sertoli Cells - metabolism
Spermatogenesis - genetics
Spermatogenesis - physiology
Transcription Factors - genetics
Transcription Factors - metabolism
Transfection
WT1 Proteins - genetics
WT1 Proteins - metabolism
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Summary: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.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad1367806