Mouse Gonad Development in the Absence of the Pro-Ovary Factor WNT4 and the Pro-Testis Factor SOX9
The transcription factors SRY and SOX9 and RSPO1/WNT4/β-Catenin signaling act as antagonistic pathways to drive testis and ovary development respectively, from a common gonadal primordium in mouse embryos. In this work, we took advantage of a double knockout mouse model to study gonadal development...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-04-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/9/5/1103 |
| _version_ | 1797569361027792896 |
|---|---|
| author | Furong Tang Nainoa Richardson Audrey Albina Marie-Christine Chaboissier Aitana Perea-Gomez |
| author_facet | Furong Tang Nainoa Richardson Audrey Albina Marie-Christine Chaboissier Aitana Perea-Gomez |
| author_sort | Furong Tang |
| collection | DOAJ |
| description | The transcription factors SRY and SOX9 and RSPO1/WNT4/β-Catenin signaling act as antagonistic pathways to drive testis and ovary development respectively, from a common gonadal primordium in mouse embryos. In this work, we took advantage of a double knockout mouse model to study gonadal development when <i>Sox9</i> and <i>Wnt4</i> are both mutated. We show that the XX gonad mutant for <i>Wnt4</i> or for both <i>Wnt4</i> and <i>Sox9</i> develop as ovotestes, demonstrating that ectopic SOX9 function is not required for the partial female-to-male sex reversal caused by a <i>Wnt4</i> mutation. <i>Sox9</i> deletion in XY gonads leads to ovarian development accompanied by ectopic WNT/β-catenin signaling. In XY <i>Sox9</i> mutant gonads, SRY-positive supporting precursors adopt a female-like identity and develop as pre-granulosa-like cells. This phenotype cannot be fully prevented by the deletion of <i>Wnt4</i> or <i>Rspo1</i>, indicating that SOX9 is required for the early determination of the male supporting cell identity independently of repressing RSPO1/WNT4/β-Catenin signaling. However, in XY <i>Sox9 Wnt4</i> double mutant gonads, pre-granulosa cells are not maintained, as they prematurely differentiate as mature granulosa cells and then trans-differentiate into Sertoli-like cells. Together, our results reveal the dynamics of the specific and independent actions of SOX9 and WNT4 during gonadal differentiation: SOX9 is essential in the testis for early specification of male-supporting cells whereas WNT4 functions in the ovary to maintain female-supporting cell identity and inhibit male-specific vascular and steroidogenic cell differentiation. |
| first_indexed | 2024-03-10T20:09:44Z |
| format | Article |
| id | doaj.art-adcc326698cf4361839aad312df0dfb1 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T20:09:44Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-adcc326698cf4361839aad312df0dfb12023-11-19T23:01:42ZengMDPI AGCells2073-44092020-04-0195110310.3390/cells9051103Mouse Gonad Development in the Absence of the Pro-Ovary Factor WNT4 and the Pro-Testis Factor SOX9Furong Tang0Nainoa Richardson1Audrey Albina2Marie-Christine Chaboissier3Aitana Perea-Gomez4CNRS, Inserm, Institut de Biologie Valrose (iBV), Université Côte d’Azur, 06108 Nice, FranceCNRS, Inserm, Institut de Biologie Valrose (iBV), Université Côte d’Azur, 06108 Nice, FranceCNRS, Inserm, Institut de Biologie Valrose (iBV), Université Côte d’Azur, 06108 Nice, FranceCNRS, Inserm, Institut de Biologie Valrose (iBV), Université Côte d’Azur, 06108 Nice, FranceCNRS, Inserm, Institut de Biologie Valrose (iBV), Université Côte d’Azur, 06108 Nice, FranceThe transcription factors SRY and SOX9 and RSPO1/WNT4/β-Catenin signaling act as antagonistic pathways to drive testis and ovary development respectively, from a common gonadal primordium in mouse embryos. In this work, we took advantage of a double knockout mouse model to study gonadal development when <i>Sox9</i> and <i>Wnt4</i> are both mutated. We show that the XX gonad mutant for <i>Wnt4</i> or for both <i>Wnt4</i> and <i>Sox9</i> develop as ovotestes, demonstrating that ectopic SOX9 function is not required for the partial female-to-male sex reversal caused by a <i>Wnt4</i> mutation. <i>Sox9</i> deletion in XY gonads leads to ovarian development accompanied by ectopic WNT/β-catenin signaling. In XY <i>Sox9</i> mutant gonads, SRY-positive supporting precursors adopt a female-like identity and develop as pre-granulosa-like cells. This phenotype cannot be fully prevented by the deletion of <i>Wnt4</i> or <i>Rspo1</i>, indicating that SOX9 is required for the early determination of the male supporting cell identity independently of repressing RSPO1/WNT4/β-Catenin signaling. However, in XY <i>Sox9 Wnt4</i> double mutant gonads, pre-granulosa cells are not maintained, as they prematurely differentiate as mature granulosa cells and then trans-differentiate into Sertoli-like cells. Together, our results reveal the dynamics of the specific and independent actions of SOX9 and WNT4 during gonadal differentiation: SOX9 is essential in the testis for early specification of male-supporting cells whereas WNT4 functions in the ovary to maintain female-supporting cell identity and inhibit male-specific vascular and steroidogenic cell differentiation.https://www.mdpi.com/2073-4409/9/5/1103gonad developmentsex determinationSOX9WNT signalingovotestis |
| spellingShingle | Furong Tang Nainoa Richardson Audrey Albina Marie-Christine Chaboissier Aitana Perea-Gomez Mouse Gonad Development in the Absence of the Pro-Ovary Factor WNT4 and the Pro-Testis Factor SOX9 Cells gonad development sex determination SOX9 WNT signaling ovotestis |
| title | Mouse Gonad Development in the Absence of the Pro-Ovary Factor WNT4 and the Pro-Testis Factor SOX9 |
| title_full | Mouse Gonad Development in the Absence of the Pro-Ovary Factor WNT4 and the Pro-Testis Factor SOX9 |
| title_fullStr | Mouse Gonad Development in the Absence of the Pro-Ovary Factor WNT4 and the Pro-Testis Factor SOX9 |
| title_full_unstemmed | Mouse Gonad Development in the Absence of the Pro-Ovary Factor WNT4 and the Pro-Testis Factor SOX9 |
| title_short | Mouse Gonad Development in the Absence of the Pro-Ovary Factor WNT4 and the Pro-Testis Factor SOX9 |
| title_sort | mouse gonad development in the absence of the pro ovary factor wnt4 and the pro testis factor sox9 |
| topic | gonad development sex determination SOX9 WNT signaling ovotestis |
| url | https://www.mdpi.com/2073-4409/9/5/1103 |
| work_keys_str_mv | AT furongtang mousegonaddevelopmentintheabsenceoftheproovaryfactorwnt4andtheprotestisfactorsox9 AT nainoarichardson mousegonaddevelopmentintheabsenceoftheproovaryfactorwnt4andtheprotestisfactorsox9 AT audreyalbina mousegonaddevelopmentintheabsenceoftheproovaryfactorwnt4andtheprotestisfactorsox9 AT mariechristinechaboissier mousegonaddevelopmentintheabsenceoftheproovaryfactorwnt4andtheprotestisfactorsox9 AT aitanapereagomez mousegonaddevelopmentintheabsenceoftheproovaryfactorwnt4andtheprotestisfactorsox9 |