Activation of beta-catenin signaling by Rspo1 controls differentiation of the mammalian ovary.
Journal - Human molecular genetics (England )
The sex of an individual is determined by the fate of the gonad. While the expression of Sry and Sox9 is sufficient to induce male development, we here show that female differentiation requires activation of the canonical beta-catenin signaling pathway. beta-catenin activation is controlled by Rspo1 in XX gonads and Rspo1 knockout mice show masculinized gonads. Molecular analyses demonstrate an absence of female-specific activation of Wnt4 and as a consequence XY-like vascularization and steroidogenesis. Moreover, germ cells of XX knockout embryos show changes in cellular adhesions and a failure to enter XX specific meiosis. Sex cords develop around birth, when Sox9 becomes strongly activated. Thus, a balance between Sox9 and beta-catenin activation determines the fate of the gonad, with Rspo1 acting as a crucial regulator of canonical beta-catenin signaling required for female development.
|ISSN : ||1460-2083|
|Mesh Heading : ||Animals Female Gene Expression Regulation, Developmental Gene Targeting Germ Cells High Mobility Group Proteins Humans Male Mice Mice, Inbred C57BL Mice, Knockout Ovary SOX9 Transcription Factor Sex Determination (Genetics) Sex Differentiation Signal Transduction Thrombospondins Transcription Factors Wnt Proteins beta Catenin cytology physiology genetics metabolism growth & development genetics genetics metabolism genetics metabolism|
|Mesh Heading Relevant : ||Cell Differentiation Transcriptional Activation cytology metabolism metabolism|