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

Abstract	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.
Authors	Dagmar Wilhelm, Christoph Englert
Journal	Genes & development (Genes Dev) Vol. 16 Issue 14 Pg. 1839-51 (Jul 15 2002) ISSN: 0890-9369 [Print] United States
PMID	12130543 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	DNA, Complementary DNA-Binding Proteins Fushi Tarazu Transcription Factors Homeodomain Proteins LHX9 protein, human LIM-Homeodomain Proteins Lhx9 protein, mouse NR5A1 protein, human Protein Isoforms Receptors, Cytoplasmic and Nuclear Steroidogenic Factor 1 Trans-Activators Transcription Factors WT1 Proteins steroidogenic factor 1, mouse
Topics	Animals Base Sequence Binding Sites DNA, Complementary DNA-Binding Proteins (genetics) Embryonic and Fetal Development Female Fushi Tarazu Transcription Factors Gene Expression Genes, Reporter Genes, Wilms Tumor Gonads (embryology, metabolism) Homeodomain Proteins (genetics, metabolism) LIM-Homeodomain Proteins Lac Operon Male Mice Mice, Inbred C57BL Mice, Knockout Molecular Sequence Data Promoter Regions, Genetic Protein Isoforms (genetics, metabolism) Receptors, Cytoplasmic and Nuclear Sex Differentiation (physiology) Steroidogenic Factor 1 Trans-Activators (genetics, metabolism) Transcription Factors (genetics) Transcriptional Activation WT1 Proteins (genetics, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!