Loss of Wnt4 and Foxl2 leads to female-to-male sex reversal extending to germ cells

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...

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Vydané v:	Human molecular genetics Ročník 16; číslo 23; s. 2795
Hlavní autori:	Ottolenghi, Chris, Pelosi, Emanuele, Tran, Joseph, Colombino, Maria, Douglass, Eric, Nedorezov, Timur, Cao, Antonio, Forabosco, Antonino, Schlessinger, David
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	England 01.12.2007
Predmet:	Animals Animals, Newborn Disorders of Sex Development Female Forkhead Box Protein L2 Forkhead Transcription Factors - deficiency Forkhead Transcription Factors - genetics Forkhead Transcription Factors - metabolism Germ Cells - cytology Germ Cells - metabolism Humans Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Models, Biological Ovary - cytology Ovary - embryology Pregnancy Sex Determination Processes Sex Differentiation Testis - cytology Testis - embryology Wnt Proteins - deficiency Wnt Proteins - genetics Wnt Proteins - metabolism Wnt4 Protein
ISSN:	0964-6906
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Shrnutí:	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 sex determination in mammals. The two genes are independently expressed and show complementary roles in ovary morphogenesis. In addition, forced expression of Foxl2 impairs testis tubule differentiation in XY transgenic mice, and germ cell-depleted XX mice lacking Foxl2 and harboring a Kit mutation undergo partial female-to-male sex reversal. The results are all consistent with an anti-testis role for Foxl2. The data suggest that the relative autonomy of the action of Foxl2, Wnt4 and additional ovarian factor(s) in the mouse should facilitate the dissection of their respective contributions to female sex determination.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0964-6906
DOI:	10.1093/hmg/ddm235