Novel insights into the regulation of LATS2 kinase in prehierarchical follicle development via the Hippo pathway in hen ovary

ABSTRACT: The large tumor suppressor homolog 2 (LATS2), one of the central regulators of the Hippo/MST signaling pathway, plays an inhibitory role in ovarian function and different organ development and growth in mammals. However, the exact roles and molecular regulatory mechanisms of LATS2 in chick...

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Autores principales:	Xue Sun, Xiaotian Niu, Ning Qin, Xuesong Shan, Jinghua Zhao, Chang Ma, Rifu Xu, Birendra Mishra
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	chicken LATS2 prehierarchical follicle Hippo pathway ovary development Animal culture SF1-1100
Acceso en línea:	https://doaj.org/article/274765c7bd5e4eb7bdd5617526155c2c
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spelling	oai:doaj.org-article:274765c7bd5e4eb7bdd5617526155c2c2021-11-24T04:21:46ZNovel insights into the regulation of LATS2 kinase in prehierarchical follicle development via the Hippo pathway in hen ovary0032-579110.1016/j.psj.2021.101454https://doaj.org/article/274765c7bd5e4eb7bdd5617526155c2c2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0032579121004776https://doaj.org/toc/0032-5791ABSTRACT: The large tumor suppressor homolog 2 (LATS2), one of the central regulators of the Hippo/MST signaling pathway, plays an inhibitory role in ovarian function and different organ development and growth in mammals. However, the exact roles and molecular regulatory mechanisms of LATS2 in chicken granulosa cell (GC) proliferation, differentiation, and steroidogenesis required for ovarian follicle growth, development, and follicular selection remain poorly understood. This study demonstrated that the LATS2 protein was predominantly localized in the oocytes and undifferentiated GCs of various-sized prehierarchical follicles of the hen ovary. Expression levels of LATS2 mRNA were significantly higher in the smaller follicles (from 1 mm to 5.9 mm in diameter) and the GCs than in the larger follicles (6–6.9 mm in diameter up to F1). Moreover, we found that high levels of LATS2 suppressed the GC proliferation and the mRNA and protein expression of the genes serving as the biomarkers of follicle selection, GC differentiation, and steroidogenesis in the GCs, including FSHR, STAR, CYP11A1, ESR1, and ESR2. Interestingly, the LATS2 significantly downregulated SAV1 and YAP1 transcripts but upregulated the expression of STK3, STK4, TEAD1, and TEAD3 mRNA. Our study provided evidences that STK3/4-LATS2-YAP1 not only acts as a suppressor of cell proliferation and follicle selection but also LATS2 may serve as an enhancer in cell proliferation and follicle selection through the YAP1-LATS2 and the LATS2-STK3/4 feedback loops by promoting the expression of TEAD1/3 but inhibiting the expression of SAV1 transcripts in the prehierarchical follicle development of hen ovary. Taken together, the present study initially revealed the pivotal role and molecular mechanism of LATS2 in the regulation of hen prehierarchical follicle development by controlling GC proliferation, differentiation, steroidogenesis, and follicle selection via the Hippo/MST signaling pathway.Xue SunXiaotian NiuNing QinXuesong ShanJinghua ZhaoChang MaRifu XuBirendra MishraElsevierarticlechickenLATS2prehierarchical follicleHippo pathwayovary developmentAnimal cultureSF1-1100ENPoultry Science, Vol 100, Iss 12, Pp 101454- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	chicken LATS2 prehierarchical follicle Hippo pathway ovary development Animal culture SF1-1100
spellingShingle	chicken LATS2 prehierarchical follicle Hippo pathway ovary development Animal culture SF1-1100 Xue Sun Xiaotian Niu Ning Qin Xuesong Shan Jinghua Zhao Chang Ma Rifu Xu Birendra Mishra Novel insights into the regulation of LATS2 kinase in prehierarchical follicle development via the Hippo pathway in hen ovary
description	ABSTRACT: The large tumor suppressor homolog 2 (LATS2), one of the central regulators of the Hippo/MST signaling pathway, plays an inhibitory role in ovarian function and different organ development and growth in mammals. However, the exact roles and molecular regulatory mechanisms of LATS2 in chicken granulosa cell (GC) proliferation, differentiation, and steroidogenesis required for ovarian follicle growth, development, and follicular selection remain poorly understood. This study demonstrated that the LATS2 protein was predominantly localized in the oocytes and undifferentiated GCs of various-sized prehierarchical follicles of the hen ovary. Expression levels of LATS2 mRNA were significantly higher in the smaller follicles (from 1 mm to 5.9 mm in diameter) and the GCs than in the larger follicles (6–6.9 mm in diameter up to F1). Moreover, we found that high levels of LATS2 suppressed the GC proliferation and the mRNA and protein expression of the genes serving as the biomarkers of follicle selection, GC differentiation, and steroidogenesis in the GCs, including FSHR, STAR, CYP11A1, ESR1, and ESR2. Interestingly, the LATS2 significantly downregulated SAV1 and YAP1 transcripts but upregulated the expression of STK3, STK4, TEAD1, and TEAD3 mRNA. Our study provided evidences that STK3/4-LATS2-YAP1 not only acts as a suppressor of cell proliferation and follicle selection but also LATS2 may serve as an enhancer in cell proliferation and follicle selection through the YAP1-LATS2 and the LATS2-STK3/4 feedback loops by promoting the expression of TEAD1/3 but inhibiting the expression of SAV1 transcripts in the prehierarchical follicle development of hen ovary. Taken together, the present study initially revealed the pivotal role and molecular mechanism of LATS2 in the regulation of hen prehierarchical follicle development by controlling GC proliferation, differentiation, steroidogenesis, and follicle selection via the Hippo/MST signaling pathway.
format	article
author	Xue Sun Xiaotian Niu Ning Qin Xuesong Shan Jinghua Zhao Chang Ma Rifu Xu Birendra Mishra
author_facet	Xue Sun Xiaotian Niu Ning Qin Xuesong Shan Jinghua Zhao Chang Ma Rifu Xu Birendra Mishra
author_sort	Xue Sun
title	Novel insights into the regulation of LATS2 kinase in prehierarchical follicle development via the Hippo pathway in hen ovary
title_short	Novel insights into the regulation of LATS2 kinase in prehierarchical follicle development via the Hippo pathway in hen ovary
title_full	Novel insights into the regulation of LATS2 kinase in prehierarchical follicle development via the Hippo pathway in hen ovary
title_fullStr	Novel insights into the regulation of LATS2 kinase in prehierarchical follicle development via the Hippo pathway in hen ovary
title_full_unstemmed	Novel insights into the regulation of LATS2 kinase in prehierarchical follicle development via the Hippo pathway in hen ovary
title_sort	novel insights into the regulation of lats2 kinase in prehierarchical follicle development via the hippo pathway in hen ovary
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/274765c7bd5e4eb7bdd5617526155c2c
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Novel insights into the regulation of LATS2 kinase in prehierarchical follicle development via the Hippo pathway in hen ovary

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