2007
DOI: 10.1093/hmg/ddm235
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Loss of Wnt4 and Foxl2 leads to female-to-male sex reversal extending to germ cells

Abstract: The discovery that the SRY gene induces male sex in humans and other mammals led to speculation about a possible equivalent for female sex. However, only partial effects have been reported for candidate genes experimentally tested so far. Here we demonstrate that inactivation of two ovarian somatic factors, Wnt4 and Foxl2, produces testis differentiation in XX mice, resulting in the formation of testis tubules and spermatogonia. These genes are thus required to initiate or maintain all major aspects of female … Show more

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Cited by 304 publications
(263 citation statements)
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“…[2,26] Interestingly, Foxl2 single mutants do not show this molecular phenotype that early. However, it is known that Foxl2 ablation up-regulates Sox9 expression postnatally.…”
Section: Foxl2: a Molecular Actor In The Spotlightmentioning
confidence: 99%
“…[2,26] Interestingly, Foxl2 single mutants do not show this molecular phenotype that early. However, it is known that Foxl2 ablation up-regulates Sox9 expression postnatally.…”
Section: Foxl2: a Molecular Actor In The Spotlightmentioning
confidence: 99%
“…While Wnt/β-catenin signaling is an important pathway in female ovarian determination, growing evidence suggests that other ovarian genes, such as Foxl2 are also important for ovarian development (Ottolenghi et al, 2007). Foxl2 has been a candidate gene responsible, when deleted, for XX sex-reversal in goats (Pailhoux et al, 2001) and it is expressed in ovarian tissue present in sex-reversed patients (Hersmus et al, 2008).…”
Section: Is Wnt/β-catenin the Proposed "Z" Factor?mentioning
confidence: 99%
“…Foxl2 has been a candidate gene responsible, when deleted, for XX sex-reversal in goats (Pailhoux et al, 2001) and it is expressed in ovarian tissue present in sex-reversed patients (Hersmus et al, 2008). Interestingly, in mice lacking genes relevant to the Wnt/β-catenin pathway, namely Rspo1 and Wnt4, Foxl2 expression is not changed which suggests that Foxl2 is acting independently of the Wnt/β-catenin pathway (Chassot et al, 2008, Ottolenghi et al, 2007. This suggests that multiple independent signals are involved in ovarian development as part of an "ovary organizer" (Ottolenghi et al, 2007).…”
Section: Is Wnt/β-catenin the Proposed "Z" Factor?mentioning
confidence: 99%
See 1 more Smart Citation
“…This is illustrated by the recent analysis of the combined double KO of Wnt4 and FoxL2 conducting to XY sex reversal. Interestingly, either gene cannot reproduce such a clear-cut phenotype in mice (Ottolenghi et al, 2007). The disruption of Figa (Soyal et al, 2000), Wnt4 (Vainio et al, 1999), Nobox (Rajkovic et al, 2004) and Gdf9 (Dong et al, 1996) explain to various extents the onset of poor or absent fertility.…”
Section: Experimental Models For a Better Understanding Of Fertility mentioning
confidence: 99%