Wnt Signaling in Ovarian Development Inhibits Sf1 Activation of Sox9 via the Tesco Enhancer
Autor: | Daniel Peter Czech, Helena Sim, Peter Koopman, Andrew H. Sinclair, Vincent R. Harley, Janelle Ryan, Pascal Bernard |
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Rok vydání: | 2012 |
Předmět: |
Anti-Mullerian Hormone
Male Steroidogenic factor 1 endocrine system medicine.medical_specialty SOX9 Biology Steroidogenic Factor 1 Mice Endocrinology Internal medicine Testis medicine Animals Cholesterol Side-Chain Cleavage Enzyme RNA Messenger Enhancer RSPO1 beta Catenin Regulation of gene expression Ovary Wnt signaling pathway Gene Expression Regulation Developmental LRP6 SOX9 Transcription Factor LRP5 Sex Determination Processes Sex-Determining Region Y Protein Wnt Proteins Cancer research Female Protein Binding Signal Transduction |
Zdroj: | Endocrinology. 153:901-912 |
ISSN: | 1945-7170 0013-7227 |
DOI: | 10.1210/en.2011-1347 |
Popis: | Genome analysis of patients with disorders of sex development, and gain- and 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 by repressing the expression of the Sertoli cell-specific gene Sox9 by an unknown mechanism. Using cell and embryonic gonad culture models, we show that activation of the Wnt/β-catenin pathway inhibits the expression of Sox9 and Amh, whereas mRNA and protein levels of Sry and steroidogenic factor 1 (Sf1), two key transcriptional regulators of Sox9, are not altered. Ectopic activation of Wnt/β-catenin signaling in male gonads led to a loss of Sf1 binding to the Tesco enhancer and absent Sox9 expression that we also observed in wild-type ovaries. Moreover, ectopic Wnt/β-catenin signaling induced the expression of the female somatic cell markers, Bmp2 and Rspo1, as a likely consequence of Sox9 loss. Wnt/β-catenin signaling in XY gonads did not, however, affect gene expression of the steroidogenic Leydig cell Sf1 target gene, Cyp11a1, or Sf1 binding to the Cyp11a1 promoter. Our data support a model in ovary development whereby activation of β-catenin prevents Sf1 binding to the Sox9 enhancer, thereby inhibiting Sox9 expression and Sertoli cell differentiation. |
Databáze: | OpenAIRE |
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