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.
Highlights
Rearrangement of the cytoskeleton during cell proliferation, differentiation and apoptosis[19,20,21]
Results from these studies provide evidence that GAS2 is a novel regulator of the formation and function of ovarian follicles, and that it is indispensible for female fertility
Using a genetically engineered mouse model, we investigated the in vivo functions of a novel regulator during follicle development, GAS2
Summary
Rearrangement of the cytoskeleton during cell proliferation, differentiation and apoptosis[19,20,21]. There are three types of follicle cells in the fly, polar cells, stalk cells and epithelial cells Their migration, differentiation and proliferation is critical for the formation of egg chambers and the generation of healthy follicles[25]. These follicle cells are not exact structural and functional parallels to the cells that compose mammalian follicles, egg chamber formation in the fly has provided an invaluable tool and model to understand key components of mammalian ovary organogenesis[26] These key components include, but are not limited to, cell-cell communications between germ cells and somatic cells, individual and collective cell migration, changes in ECM, cell adhesion and cell shape during follicle growth, and the signaling pathways that regulate these processes[27]. Results from these studies provide evidence that GAS2 is a novel regulator of the formation and function of ovarian follicles, and that it is indispensible for female fertility
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