title: The Hippo/MST Pathway Member SAV1 Plays a Suppressive Role in Development of the Prehierarchical Follicles in Hen Ovary.
abstract: The Hippo/MST signaling pathway is a critical player in controlling cell proliferation, self-renewal, differentiation, and apoptosis of most tissues and organs in diverse species. Previous studies have shown that Salvador homolog 1 (SAV1), a scaffolding protein which functions in the signaling system is expressed in mammalian ovaries and play a vital role in governing the follicle development. But the exact biological effects of chicken SAV1 in prehierarchical follicle development remain poorly understood. In the present study, we demonstrated that the SAV1 protein is predominantly expressed in the oocytes and undifferentiated granulosa cells in the various sized prehierarchical follicles of hen ovary, and the endogenous expression level of SAV1 mRNA appears down-regulated from the primordial follicles to the largest preovulatory follicles (F2-F1) by immunohistochemistry and real-time RT-PCR, respectively. Moreover, we found the intracellular SAV1 physically interacts with each of the pathway members, including STK4/MST1, STK3/MST2, LATS1 and MOB2 using western blotting. And SAV1 significantly promotes the phosphorylation of LATS1 induced by the kinase of STK4 or STK3 in vitro. Furthermore, SAV1 knockdown by small interfering RNA (siRNA) significantly increased proliferation of granulosa cells from the prehierarchical follicles (6-8 mm in diameter) by BrdU-incorporation assay, in which the expression levels of GDF9, StAR and FSHR mRNA was notably enhanced. Meanwhile, these findings were consolidated by the data of SAV1 overexpression. Taken together, the present results revealed that SAV1 can inhibit proliferation of the granulosa cells whereby the expression levels of GDF9, StAR and FSHR mRNA were negatively regulated. Accordingly, SAV1, as a member of the hippo/MST signaling pathway plays a suppressive role in ovarian follicle development by promoting phosphorylation and activity of the downstream LATS1, may consequently lead to prevention of the follicle selection during ovary development.
authors: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, Jilin, China.
authors: Zhichao
authors: Z
authors: Lyu
authors: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, Jilin, China.
authors: Ning
authors: N
authors: Qin
authors: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, Jilin, China.
authors: Thobela Louis
authors: TL
authors: Tyasi
authors: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, Jilin, China.
authors: Hongyan
authors: H
authors: Zhu
authors: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, Jilin, China.
authors: Dehui
authors: D
authors: Liu
authors: Jilin Grain Group Agriculture and Livestock Co., Ltd., Changchun 130062, Jilin, China.
authors: Shuguo
authors: S
authors: Yuan
authors: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, Jilin, China.
authors: Rifu
authors: R
authors: Xu
mesh_terms: D000818:Animals; D016466:CHO Cells; D018797:Cell Cycle Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002645:Chickens; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006107:Granulosa Cells / Q000166:cytology; D006080:Ovarian Follicle / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction
chemical_list: D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt