Lats1 and Lats2 regulate YAP and TAZ activity to control the development of mouse Sertoli cells.
FASEB J
; 38(9): e23633, 2024 May 15.
Article
em En
| MEDLINE
| ID: mdl-38690712
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.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Células de Sertoli
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Diferenciação Celular
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Proteínas Serina-Treonina Quinases
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Proteínas Supressoras de Tumor
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Proteínas Adaptadoras de Transdução de Sinal
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Proteínas de Sinalização YAP
Limite:
Animals
Idioma:
En
Revista:
FASEB J
Assunto da revista:
BIOLOGIA
/
FISIOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Canadá