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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Veröffentlicht in:Human molecular genetics Jg. 16; H. 23; S. 2795
Hauptverfasser: Ottolenghi, Chris, Pelosi, Emanuele, Tran, Joseph, Colombino, Maria, Douglass, Eric, Nedorezov, Timur, Cao, Antonio, Forabosco, Antonino, Schlessinger, David
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England 01.12.2007
Schlagworte:
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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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0964-6906
DOI:10.1093/hmg/ddm235