Wnt Signaling in Ovarian Development Inhibits Sf1 Activation of Sox9 via the Tesco Enhancer

• DOI: 10.1210/en.2011-1347
• Publication Date: 2011-12-01T14:28:30Z
• Authors: Pascal Bernard; Janelle Ryan; Helena Sim; Daniel P. Czech; Andrew H. Sinclair; Peter Koopman; Vincent R. Harley
• Keywords: SOX9; Steroidogenic factor 1; Ectopic expression; Testis determining factor

Genome analysis of patients with disorders sex development, and gain- loss-of-function studies in mice indicate that gonadal development is regulated by opposing signals. In females, the Wnt/β-catenin canonical pathway blocks testicular differentiation repressing expression Sertoli cell-specific gene Sox9 an unknown mechanism. Using cell embryonic gonad culture models, we show activation inhibits Amh, whereas mRNA protein levels Sry steroidogenic factor 1 (Sf1), two key transcriptional regulators Sox9, are not altered. Ectopic signaling male gonads led to a loss Sf1 binding Tesco enhancer absent also observed wild-type ovaries. Moreover, ectopic induced female somatic markers, Bmp2 Rspo1, as likely consequence loss. XY did not, however, affect Leydig target gene, Cyp11a1, or Cyp11a1 promoter. Our data support model ovary whereby β-catenin prevents enhancer, thereby inhibiting differentiation.