Sox9/β-catenin Double Knockout Mice Uncover a New Paradigm in Testis Differentiation

Monday, September 22, 2014 — Poster Session I
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NIEHS	DEVBIO-6

* FARE Award Winner

Authors

• B. Nicol
• H. Yao

Abstract

In mammals, testis and ovary arise from the embryonic bipotential gonad, whose fate hinges upon the balance between pro-testis SOX9 and pro-ovary ß-catenin. Then, what does the bipotential gonad become when both SOX9 and β-catenin are absent? To answer this question, we ablated SOX9 and ß-catenin in the somatic cells of bipotential gonads and we compared the phenotype and transcriptome of Sox9/ß-catenin double knockout (DKO) to ß-catenin and Sox9 single knockout (KO) and control mouse embryos. The XX DKO gonads present the same partial ovary-to-testis sex reversal than the ß-cateninKO gonads, indicating that Sox9 is not responsible for this masculinization. The XY DKO gonads form ovotestes, a less severe phenotype than the complete testis-to-ovary sex reversal in the XY Sox9KO. Intriguingly, the XY DKO gonads developed more prominent testis characteristics than the XX DKO gonads. This leads to a provocative hypothesis that in addition to stimulating Sox9 expression, Sry may also induce other unknown pro-testis genes. Our novel findings shed new light on the complex antagonisms between pro-ovary and pro-testis pathways. While testis differentiation was thought to be the result of a direct induction by SOX9, we show here that it actually requires both Sox9-dependent and -independent morphogenetic changes.

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