A conserved function of Human DLC3 and Drosophila Cv-c in testis development
The identification of genes affecting gonad development is essential to understand the mechanisms causing Variations/Differences in Sex Development (DSD). Recently, a DLC3 mutation was associated with male gonadal dysgenesis in 46,XY DSD patients. We have studied the requirement of Cv-c, the Drosoph...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/82343 |
| _version_ | 1811179680109166592 |
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| author | Sol Sotillos Isabel von der Decken Ivan Domenech Mercadé Sriraksha Srinivasan Dmytro Sirokha Ludmila Livshits Stefano Vanni Serge Nef Anna Biason-Lauber Daniel Rodríguez Gutiérrez James Castelli-Gair Hombría |
| author_facet | Sol Sotillos Isabel von der Decken Ivan Domenech Mercadé Sriraksha Srinivasan Dmytro Sirokha Ludmila Livshits Stefano Vanni Serge Nef Anna Biason-Lauber Daniel Rodríguez Gutiérrez James Castelli-Gair Hombría |
| author_sort | Sol Sotillos |
| collection | DOAJ |
| description | The identification of genes affecting gonad development is essential to understand the mechanisms causing Variations/Differences in Sex Development (DSD). Recently, a DLC3 mutation was associated with male gonadal dysgenesis in 46,XY DSD patients. We have studied the requirement of Cv-c, the Drosophila ortholog of DLC3, in Drosophila gonad development, as well as the functional capacity of DLC3 human variants to rescue cv-c gonad defects. We show that Cv-c is required to maintain testis integrity during fly development. We find that Cv-c and human DLC3 can perform the same function in fly embryos, as flies carrying wild type but not patient DLC3 variations can rescue gonadal dysgenesis, suggesting functional conservation. We also demonstrate that the StART domain mediates Cv-c's function in the male gonad independently from the GAP domain's activity. This work demonstrates a role for DLC3/Cv-c in male gonadogenesis and highlights a novel StART domain mediated function required to organize the gonadal mesoderm and maintain its interaction with the germ cells during testis development. |
| first_indexed | 2024-04-11T06:38:44Z |
| format | Article |
| id | doaj.art-ebe1bdd874904a7ca1e61e60f5dd9b1b |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T06:38:44Z |
| publishDate | 2022-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-ebe1bdd874904a7ca1e61e60f5dd9b1b2022-12-22T04:39:37ZengeLife Sciences Publications LtdeLife2050-084X2022-11-011110.7554/eLife.82343A conserved function of Human DLC3 and Drosophila Cv-c in testis developmentSol Sotillos0https://orcid.org/0000-0003-4731-8107Isabel von der Decken1Ivan Domenech Mercadé2https://orcid.org/0000-0003-2115-8475Sriraksha Srinivasan3Dmytro Sirokha4Ludmila Livshits5Stefano Vanni6https://orcid.org/0000-0003-2146-1140Serge Nef7https://orcid.org/0000-0001-5462-0676Anna Biason-Lauber8https://orcid.org/0000-0001-8966-2913Daniel Rodríguez Gutiérrez9https://orcid.org/0000-0002-2979-0769James Castelli-Gair Hombría10https://orcid.org/0000-0003-4183-5250Centro Andaluz de Biología del Desarrollo, Seville, SpainDepartment of Endocrinology, Metabolism and Cardiovascular research, University of Fribourg, Fribourg, SwitzerlandDepartment of Endocrinology, Metabolism and Cardiovascular research, University of Fribourg, Fribourg, SwitzerlandDepartment of Biology, University of Fribourg, Fribourg, SwitzerlandInstitute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv, UkraineInstitute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv, UkraineDepartment of Biology, University of Fribourg, Fribourg, SwitzerlandDepartment of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, SwitzerlandDepartment of Endocrinology, Metabolism and Cardiovascular research, University of Fribourg, Fribourg, SwitzerlandDepartment of Endocrinology, Metabolism and Cardiovascular research, University of Fribourg, Fribourg, SwitzerlandCentro Andaluz de Biología del Desarrollo, Seville, SpainThe identification of genes affecting gonad development is essential to understand the mechanisms causing Variations/Differences in Sex Development (DSD). Recently, a DLC3 mutation was associated with male gonadal dysgenesis in 46,XY DSD patients. We have studied the requirement of Cv-c, the Drosophila ortholog of DLC3, in Drosophila gonad development, as well as the functional capacity of DLC3 human variants to rescue cv-c gonad defects. We show that Cv-c is required to maintain testis integrity during fly development. We find that Cv-c and human DLC3 can perform the same function in fly embryos, as flies carrying wild type but not patient DLC3 variations can rescue gonadal dysgenesis, suggesting functional conservation. We also demonstrate that the StART domain mediates Cv-c's function in the male gonad independently from the GAP domain's activity. This work demonstrates a role for DLC3/Cv-c in male gonadogenesis and highlights a novel StART domain mediated function required to organize the gonadal mesoderm and maintain its interaction with the germ cells during testis development.https://elifesciences.org/articles/8234346,XY gonadal dysgenesishuman gonadogenesisDrosophila testisdeleted in liver cancer/Cv-cStART-RhoGAP domain |
| spellingShingle | Sol Sotillos Isabel von der Decken Ivan Domenech Mercadé Sriraksha Srinivasan Dmytro Sirokha Ludmila Livshits Stefano Vanni Serge Nef Anna Biason-Lauber Daniel Rodríguez Gutiérrez James Castelli-Gair Hombría A conserved function of Human DLC3 and Drosophila Cv-c in testis development eLife 46,XY gonadal dysgenesis human gonadogenesis Drosophila testis deleted in liver cancer/Cv-c StART-RhoGAP domain |
| title | A conserved function of Human DLC3 and Drosophila Cv-c in testis development |
| title_full | A conserved function of Human DLC3 and Drosophila Cv-c in testis development |
| title_fullStr | A conserved function of Human DLC3 and Drosophila Cv-c in testis development |
| title_full_unstemmed | A conserved function of Human DLC3 and Drosophila Cv-c in testis development |
| title_short | A conserved function of Human DLC3 and Drosophila Cv-c in testis development |
| title_sort | conserved function of human dlc3 and drosophila cv c in testis development |
| topic | 46,XY gonadal dysgenesis human gonadogenesis Drosophila testis deleted in liver cancer/Cv-c StART-RhoGAP domain |
| url | https://elifesciences.org/articles/82343 |
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