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Development, Vol 119, Issue 4 1329-1341, Copyright © 1993 by Company of Biologists
JOURNAL ARTICLES |
S Mundlos, J Pelletier, A Darveau, M Bachmann, A Winterpacht and B Zabel
Department of Pediatrics, University of Mainz, Germany.
The human Wilms' tumor gene WT1 encodes a putative transcription factor implicated in tumorigenesis and in specifying normal urogenital development. We have studied the distribution of WT1 protein and mRNA using immunohistochemistry and in situ hybridization. Monoclonal antibodies were raised against a peptide specific to the first alternative splice site of WT1. Two antibodies specifically reacted on Western blot to this WT1 isoform. Immunofluorescence localized WT1 protein to podocytes during mesonephric and metanephric development. In situ hybridization revealed a similar pattern of expression except that WT1 mRNA was also present in metanephric blastema and renal vesicles. Messenger RNA expression was most pronounced in the kidneys during early fetal development and declined thereafter. In contrast, WT1 protein was readily detectable in glomerular podocytes throughout adulthood. WT1 protein in Wilms' tumor was present in blastema and glomeruloid structures. Expression in the female gonad was linked to the different stages of granulosa cell development. In the male gonad, expression was restricted to Sertoli cells and their precursors, the embryonic tunica albuginea and the rete testis. The intracellular distribution of the WT1 protein was investigated by confocal laser microscopy and was demonstrated to be exclusively nuclear. The nuclear distribution and the selective pattern of expression support the proposed role of WT1 as a transcription factor active during urogenital development. The persistence of WT1 expression in the adult kidney suggests a role in homeostasis of the podocyte.
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V. Schumacher, S. Schneider, A. Figge, G. Wildhardt, D. Harms, D. Schmidt, A. Weirich, R. Ludwig, and B. Royer-Pokora Correlation of germ-line mutations and two-hit inactivation of the WT1 gene with Wilms tumors of stromal-predominant histology PNAS, April 15, 1997; 94(8): 3972 - 3977. [Abstract] [Full Text] [PDF]
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W. Bruening and J. Pelletier A Non-AUG Translational Initiation Event Generates Novel WT1 Isoforms J. Biol. Chem., April 12, 1996; 271(15): 8646 - 8654. [Abstract] [Full Text] [PDF]
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J. C. Reddy, J. C. Morris, J. Wang, M. A. English, D. A. Haber, Y. Shi, and J. D. Licht WT1-mediated Transcriptional Activation Is Inhibited by Dominant Negative Mutant Proteins J. Biol. Chem., May 5, 1995; 270(18): 10878 - 10884. [Abstract] [Full Text] [PDF]
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