Tissue-specific RNAi Reveals That WT1 Expression in Nurse Cells Controls Germ Cell Survival and Spermatogenesis

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2006 Jan 19

PMID 16418481

Citations 50

Authors

Manjeet K Rao

John Pham

J Saadi Imam

James A MacLean

Deepa Murali

Yasuhide Furuta

Amiya P Sinha-Hikim

Miles F Wilkinson

Affiliations

Soon will be listed here.

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.

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