Wilms tumor protein–dependent transcription of VEGF receptor 2 and hypoxia regulate expression of the testis-promoting gene Sox9 in murine embryonic gonads

• DOI: 10.1074/jbc.m117.816751
• Publication Date: 2017-10-17T19:15:26Z
• Authors: Karin M. Kirschner; Lina K. Sciesielski; Katharina Krueger; Holger Scholz
• Keywords: SOX9; Chromatin immunoprecipitation

Wilms tumor protein 1 (WT1) has been implicated in the control of several genes sexual development, but its function gonad formation is still unclear. Here, we report that WT1 stimulates expression Kdr, gene encoding VEGF receptor 2, murine embryonic gonads. We found and KDR are co-expressed Sertoli cells testes somatic ovaries. Vivo-morpholino–mediated knockdown decreased Kdr transcripts cultured gonads at multiple developmental stages. Furthermore, bound to promoter chromatin Forced WT1(−KTS) isoform, which functions as a transcription factor, increased mRNA levels, whereas WT1(+KTS) acts presumably on post-transcriptional level, did not. ChIP indicated WT1(−KTS), not WT1(+KTS), binds promoter. Treatment with tyrosine kinase inhibitor SU1498 or ligand VEGFA revealed signaling represses testis-promoting Sox9 XX abrogated stimulatory effect SU1498-mediated inhibition expression. Exposure 1% O2 mimic low-oxygen conditions embryo Vegfa affect levels gonadal explants. However, incubation presence significantly reduced These findings demonstrate both local oxygen environment WT1, enhances expression, contribute sex-specific developing