1. Lats1 and Lats2 regulate YAP and TAZ activity to control the development of mouse Sertoli cells.
- Author
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Abou Nader N, Charrier L, Meisnsohn MC, Banville L, Deffrennes B, St-Jean G, Boerboom D, Zamberlam G, Brind'Amour J, Pépin D, and Boyer A
- Subjects
- Animals, Male, Mice, Mice, Knockout, Signal Transduction, Cell Cycle Proteins metabolism, Cell Cycle Proteins genetics, Testis metabolism, Epithelial-Mesenchymal Transition physiology, Transcription Factors metabolism, Transcription Factors genetics, Acyltransferases genetics, Acyltransferases metabolism, Transcriptional Coactivator with PDZ-Binding Motif Proteins metabolism, Trans-Activators metabolism, Trans-Activators genetics, Sertoli Cells metabolism, Protein Serine-Threonine Kinases metabolism, Protein Serine-Threonine Kinases genetics, YAP-Signaling Proteins metabolism, Adaptor Proteins, Signal Transducing metabolism, Adaptor Proteins, Signal Transducing genetics, Tumor Suppressor Proteins metabolism, Tumor Suppressor Proteins genetics, Cell Differentiation physiology
- Abstract
Recent reports suggest that the Hippo signaling pathway regulates testis development, though its exact roles in Sertoli cell differentiation remain unknown. Here, we examined the functions of the main Hippo pathway kinases, large tumor suppressor homolog kinases 1 and 2 (Lats1 and Lats2) in developing mouse Sertoli cells. Conditional inactivation of Lats1/2 in Sertoli cells resulted in the disorganization and overgrowth of the testis cords, the induction of a testicular inflammatory response and germ cell apoptosis. Stimulated by retinoic acid 8 (STRA8) expression in germ cells additionally suggested that germ cells may have been preparing to enter meiosis prior to their loss. Gene expression analyses of the developing testes of conditional knockout animals further suggested impaired Sertoli cell differentiation, epithelial-to-mesenchymal transition, and the induction of a specific set of genes associated with Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ)-mediated integrin signaling. Finally, the involvement of YAP/TAZ in Sertoli cell differentiation was confirmed by concomitantly inactivating Yap/Taz in Lats1/2 conditional knockout model, which resulted in a partial rescue of the testicular phenotypic changes. Taken together, these results identify Hippo signaling as a crucial pathway for Sertoli cell development and provide novel insight into Sertoli cell fate maintenance., (© 2024 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)
- Published
- 2024
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