The Wilms tumor suppressor WT1 regulates early gonad development by activation of Sf1
Abstract
In mammals, several genes including the Wilms tumor suppressor geneWt1, the Lim homeobox gene Lhx9, and the gene encoding steroidogenic factor 1 (Sf1) have been implicated in the development of the indifferent gonad prior to sexual differentiation. Interactions among these genes have not yet been elucidated. Using biochemical and genetic experiments, we demonstrate here that WT1 and LHX9 function as direct activators of the Sf1 gene. Interestingly, only the −KTS form of WT1 is able to bind to and transactivate the Sf1 promoter. This observation is consistent with differential roles for the −KTS and +KTS variants of WT1 which have been postulated on the basis of human disorders such as the Frasier syndrome. Our data suggest a pathway in which the products of the Wt1 and Lhx9 genes activate expression ofSf1 and thus mediate early gonadogenesis.
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Footnotes
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Present addresses: 1Institute for Molecular Bioscience, The University of Queensland, Brisbane Qld 4072, Australia; 2Biozentrum der Universität Würzburg, Lehrstuhl für Physiologische Chemie I, Am Hubland, 97074 Würzburg, Germany.
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↵3 Corresponding author.
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E-MAIL cenglert{at}biozentrum.uni-wuerzburg.de; FAX 49-931-888-4150.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.220102.
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- Received November 13, 2001.
- Accepted May 28, 2002.
- Cold Spring Harbor Laboratory Press
