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 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.
Rao
Manjeet K
MK
Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Pham
John
J
Imam
J Saadi
JS
MacLean
James A
JA
Murali
Deepa
D
Furuta
Yasuhide
Y
Sinha-Hikim
Amiya P
AP
Wilkinson
Miles F
MF
D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D004257:DNA Polymerase II / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005854:Germ Cells / Q000201:enzymology / Q000502:physiology*; D006066:Gonads / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009928:Organ Specificity; D034622:RNA Interference; D012322:RNA Precursors / Q000378:metabolism; D015203:Reproducibility of Results; D043244:Ribonuclease III / Q000378:metabolism; D012708:Sertoli Cells / Q000378:metabolism*; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D025721:WT1 Proteins / Q000235:genetics* / Q000378:metabolism
D012322:RNA Precursors; D014157:Transcription Factors; D025721:WT1 Proteins; D004257:DNA Polymerase II; C517918:DROSHA protein, human; D043244:Ribonuclease III