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Lats1andLats2are required for ovarian granulosa cell fate maintenance
- Source :
- FASEB J
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- Recent reports suggest that the Hippo signaling pathway influences ovarian follicle development; however, its exact roles remain unknown. Here, we examined the ovarian functions of the Hippo kinases large tumor suppressors (LATS)1 and 2, which serve to inactivate the transcriptional coactivators Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). Inactivation of Lats1/2 in murine granulosa cells either in vitro or in vivo resulted in a loss of granulosa cell morphology, function, and gene expression. Mutant cells further underwent changes in structure and gene expression suggestive of epithelial-to-mesenchymal transition and transdifferentiation into multiple lineages. In vivo, granulosa cell–specific loss of Lats1/2 caused the ovarian parenchyma to be mostly replaced by bone tissue and seminiferous tubule-like structures. Transdifferentiation into Sertoli-like cells and osteoblasts was attributed in part to the increased recruitment of YAP and TAZ to the promoters of sex-determining region Y box 9 and bone γ-carboxyglutamate protein, key mediators of male sex determination and osteogenesis, respectively. Together, these results demonstrate for the first time a critical role for Lats1/2 in the maintenance of the granulosa cell genetic program and further highlight the remarkable plasticity of granulosa cells.—Tsoi, M., Morin, M., Rico, C., Johnson, R. L., Paquet, M., Gévry, N., Boerboom, D. Lats1 and Lats2 are required for ovarian granulosa cell fate maintenance.
- Subjects :
- 0301 basic medicine
endocrine system
Hippo signaling pathway
Ovarian Granulosa Cell
Kinase
Research
Granulosa cell
Male sex determination
Transdifferentiation
SOX9
Biology
Biochemistry
Cell biology
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
medicine.anatomical_structure
Genetics
medicine
Ovarian follicle
Molecular Biology
030217 neurology & neurosurgery
Biotechnology
Subjects
Details
- ISSN :
- 15306860 and 08926638
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- The FASEB Journal
- Accession number :
- edsair.doi.dedup.....7a6f99cbcd2a54f1161f7e84a2d93e7b