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Publication : The Wilms tumor suppressor WT1 regulates early gonad development by activation of Sf1.

First Author  Wilhelm D Year  2002
Journal  Genes Dev Volume  16
Issue  14 Pages  1839-51
PubMed ID  12130543 Mgi Jnum  J:77996
Mgi Id  MGI:2183075 Doi  10.1101/gad.220102
Citation  Wilhelm D, et al. (2002) The Wilms tumor suppressor WT1 regulates early gonad development by activation of Sf1. Genes Dev 16(14):1839-51
abstractText  In mammals, several genes including the Wilms tumor suppressor gene Wt1, 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 of Sf1 and thus mediate early gonadogenesis.
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