title: Growth Arrest Specific 2 (GAS2) is a Critical Mediator of Germ Cell Cyst Breakdown and Folliculogenesis in Mice.
abstract: In the mouse ovary, the primordial follicle pool is established through a diverse array of signaling pathways and tissue remodeling events. Growth arrest specific gene two (GAS2) is a highly conserved cytoskeleton-associated protein whose in vivo function remains unclear. In Drosophila, loss of the GAS2 homolog, Pigs, results in infertility. We demonstrate herein that, in the mouse ovary, GAS2 is expressed in the stromal cells surrounding the oocyte cysts on 16.5 dpc, and in stromal cells surrounding growing follicles during juvenile and adult life. We have generated genetically engineered mice with inactivated Gas2. Gas2 homozygous mutant mice are viable but have severely impaired fertility in females, in which oocyte cyst breakdown is disrupted and follicle growth is impaired, with significantly reduced numbers of large antral follicles and corpora lutea. In these mutant mice, the organization of the basal lamina surrounding developing follicles is severely defective at multiple stages of folliculogenesis. We also found that Notch signaling activity was altered in ovaries from Gas2 null mice around the time of birth and during follicular development later in life. These results indicate that GAS2 is a critical and novel regulator of tissue remodeling in the ovary during oocyte cyst breakdown and folliculogenesis.
authors.affiliation: Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX 77030, USA.|Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: J Philippe
authors.initials: JP
authors.lastname: York
authors.affiliation: Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Yi Athena
authors.initials: YA
authors.lastname: Ren
authors.affiliation: The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510150, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX 77030, USA.
authors.lastname: Bin Zhang
authors.affiliation: The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510150, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510150, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.affiliation: The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510150, China.
authors.forename: Jianqiao
authors.initials: J
authors.lastname: Liu
authors.affiliation: The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510150, China.|Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX 77030, USA.|Biochemistry and Molecular Biology, Baylor College of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Xia
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, 77030, USA.|Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.|Biochemistry and Molecular Biology, Baylor College of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Pumin
authors.initials: P
authors.lastname: Zhang
mesh_terms: D000483:Alleles; D000818:Animals; D005260:Female; D005298:Fertility; D005854:Germ Cells / Q000166:cytology*; D006367:HeLa Cells; D006720:Homozygote; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D006080:Ovarian Follicle / Q000502:physiology*; D010053:Ovary / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism
chemical_list: C099165:Gas2 protein, mouse; D008840:Microfilament Proteins; D051880:Receptors, Notch; D008156:Luciferases