Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination.
The genes encoding members of the wingless-related MMTV integration site (WNT) and fibroblast growth factor (FGF) families coordinate growth, morphogenesis, and differentiation in many fields of cells during development. In the mouse, Fgf9 and Wnt4 are expressed in gonads of both sexes prior to sex...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2006-06-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.0040187 |
| _version_ | 1798024998343933952 |
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| author | Yuna Kim Akio Kobayashi Ryohei Sekido Leo DiNapoli Jennifer Brennan Marie-Christine Chaboissier Francis Poulat Richard R Behringer Robin Lovell-Badge Blanche Capel |
| author_facet | Yuna Kim Akio Kobayashi Ryohei Sekido Leo DiNapoli Jennifer Brennan Marie-Christine Chaboissier Francis Poulat Richard R Behringer Robin Lovell-Badge Blanche Capel |
| author_sort | Yuna Kim |
| collection | DOAJ |
| description | The genes encoding members of the wingless-related MMTV integration site (WNT) and fibroblast growth factor (FGF) families coordinate growth, morphogenesis, and differentiation in many fields of cells during development. In the mouse, Fgf9 and Wnt4 are expressed in gonads of both sexes prior to sex determination. Loss of Fgf9 leads to XY sex reversal, whereas loss of Wnt4 results in partial testis development in XX gonads. However, the relationship between these signals and the male sex-determining gene, Sry, was unknown. We show through gain- and loss-of-function experiments that fibroblast growth factor 9 (FGF9) and WNT4 act as opposing signals to regulate sex determination. In the mouse XY gonad, Sry normally initiates a feed-forward loop between Sox9 and Fgf9, which up-regulates Fgf9 and represses Wnt4 to establish the testis pathway. Surprisingly, loss of Wnt4 in XX gonads is sufficient to up-regulate Fgf9 and Sox9 in the absence of Sry. These data suggest that the fate of the gonad is controlled by antagonism between Fgf9 and Wnt4. The role of the male sex-determining switch--Sry in the case of mammals--is to tip the balance between these underlying patterning signals. In principle, sex determination in other vertebrates may operate through any switch that introduces an imbalance between these two signaling pathways. |
| first_indexed | 2024-04-11T18:11:39Z |
| format | Article |
| id | doaj.art-3b1931093d284957bfd51355a80517d6 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-04-11T18:11:39Z |
| publishDate | 2006-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-3b1931093d284957bfd51355a80517d62022-12-22T04:10:04ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852006-06-0146e18710.1371/journal.pbio.0040187Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination.Yuna KimAkio KobayashiRyohei SekidoLeo DiNapoliJennifer BrennanMarie-Christine ChaboissierFrancis PoulatRichard R BehringerRobin Lovell-BadgeBlanche CapelThe genes encoding members of the wingless-related MMTV integration site (WNT) and fibroblast growth factor (FGF) families coordinate growth, morphogenesis, and differentiation in many fields of cells during development. In the mouse, Fgf9 and Wnt4 are expressed in gonads of both sexes prior to sex determination. Loss of Fgf9 leads to XY sex reversal, whereas loss of Wnt4 results in partial testis development in XX gonads. However, the relationship between these signals and the male sex-determining gene, Sry, was unknown. We show through gain- and loss-of-function experiments that fibroblast growth factor 9 (FGF9) and WNT4 act as opposing signals to regulate sex determination. In the mouse XY gonad, Sry normally initiates a feed-forward loop between Sox9 and Fgf9, which up-regulates Fgf9 and represses Wnt4 to establish the testis pathway. Surprisingly, loss of Wnt4 in XX gonads is sufficient to up-regulate Fgf9 and Sox9 in the absence of Sry. These data suggest that the fate of the gonad is controlled by antagonism between Fgf9 and Wnt4. The role of the male sex-determining switch--Sry in the case of mammals--is to tip the balance between these underlying patterning signals. In principle, sex determination in other vertebrates may operate through any switch that introduces an imbalance between these two signaling pathways.https://doi.org/10.1371/journal.pbio.0040187 |
| spellingShingle | Yuna Kim Akio Kobayashi Ryohei Sekido Leo DiNapoli Jennifer Brennan Marie-Christine Chaboissier Francis Poulat Richard R Behringer Robin Lovell-Badge Blanche Capel Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination. PLoS Biology |
| title | Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination. |
| title_full | Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination. |
| title_fullStr | Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination. |
| title_full_unstemmed | Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination. |
| title_short | Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination. |
| title_sort | fgf9 and wnt4 act as antagonistic signals to regulate mammalian sex determination |
| url | https://doi.org/10.1371/journal.pbio.0040187 |
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