Browsing by Subject "Oogenesis"
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Item Characterization of Ataxin 2-Binding Protein 1 During Female Germ Cell Differentiation in Drosophila Melanogaster(2010-11-02) Yilmaz, Ömür; Buszczak, MichaelIn the Drosophila ovary, the molecules that promote the continued stepwise development of germline stem cells after their exit the niche remain largely unknown. During Drosophila oogenesis, a germline stem cell (GSC) divides asymmetrically to produce a renewing stem cell and a differentiated daughter that will progress through different stages of oogenesis to produce a mature egg. Numerous factors regulate the balance between GSC and a daughter cell, the cystoblast (CB). The Dpp/BMP signaling pathway from the niche silences bam transcription, a key differentiation factor, in the GSC. Bam protein is expressed in the cystoblast and forms a complex with its partner Bgcn, to antagonize the Pumilio-Nanos (Pum-Nos) complex through nos 3’UTR. Repression of Pum-Nos activity by the Bam-Bgcn complex permits CB differentiation. The CB goes through four incomplete divisions to give rise to a 16 cell cyst that buds off from the germarium to form an egg chamber. A number of genes have been found to have roles at 16 cell stage germ cell cysts but the molecular events that govern the intermediate stages (2-, 4- and 8-cell cysts) have remained elusive. In this study, I investigated the function of Drosophila homolog of the human disease gene Ataxin 2-binding protein 1 (A2BP1) during germline cyst differentiation. Through phenotypic analysis I showed that strong A2BP1 mutants display cystic tumors and mitosis to meiosis transition defects while weaker alleles have germline counting defects. Also, by genetic and biochemical analysis, I found that A2BP1 interacts with itself and Bruno, a known translational repressor. In addition, I examined the relationship between A2BP1 protein and other differentiation genes by expression analysis and showed that A2BP1 expression bridges the expression of the early differentiation factor Bam with late markers such as Bruno, Orb and Rbp9. The expression of A2BP1 is lost in bam, snf and mei-P26 mutants but is still present in rbp9 and arrest mutants. These observations might indicate existence of a linear hierarchy between these differentiation genes. In summary, my studies revealed A2BP1 defines a new tier within the genetic hierarchy that promotes the differentiation of single germ cells into mature 16-cell cysts during Drosophila oogenesis.Item GATA Like Protein-1: A Somatic Cell Factor Required for Normal Ovarian Development and Function(2010-09-20) Strauss, Tamara Joy; Hammes, Stephen R.Oogenesis and follicular maturation are processes that require organized and precisely timed communication through paracrine and endocrine signals of neighboring tissues. Deviations in the cross talk between ovarian cells, or aberrant gene expression within one of the cell populations, can lead to germ cell loss and infertility in the adult female. Expression of Glp-1 in the somatic cells of the ovary is required for normal fertility in female mice, as a deficiency for Glp-1 leads to the absence of oocytes at birth and ovarian tubular formation in the adult. However, the nature of germ cell loss and tubular adenoma formation, in the setting of a somatic cell protein deficiency, is not well understood. In this report, I characterize the embryonic germ cell loss phenotype in Glp-1LacZ null mice. Immunohistochemical analyses of Glp-1LacZ null mouse ovaries show that germ cells are appropriately specified and migrate to the nascent gonad similarly to wild type. After their arrival at the gonad, precocious loss of the germ cells begins at or around E13.5. This loss is completed by birth and is accompanied by defects in the expression of oocyte-specific genes associated with meiotic entry. Interestingly, somatic pregranulosa cells retain their ability to secrete paracrine signaling molecules to the oocyte and are still able to form the basement membrane surrounding the germline cysts. In the adult, the structure of the germline cyst persists, albeit without germ cells, and there is loss of HPG axis communication. The loss in HPG communication in Glp-1LacZ null mice can be accounted for by loss of regulated steroidogenesis through the GATA4-dependent transcriptional activation of StAR. These data imply that the somatic cell protein Glp-1 regulates 1) germ cell survival early in embryogenesis and 2) steroidogenesis through StAR promoter activation.Item The Small GTPase Rheb Is Required for Spermatogenesis but not Oogenesis(2013-10-01) Baker, Michael David; Lum, Lawrence; Castrillon, Diego H.; Brekken, Rolf A.; Amatruda, James F.The process of germ cell development is under the tight control of various signaling pathways among which the PI3K-PKB-mTOR pathway is of critical importance. Previous studies have demonstrated sex-specific roles for several components of this pathway. In the current study I aimed to evaluate the role of Rheb, a member of the small GTPase superfamily and a critical component for mTORC1 activation, in male and female gametogenesis. The function of Rheb in development and the nervous system has been extensively studied, but little was known about its role in the germline. I have exploited genetic approaches in the mouse to study the role of Rheb in the germline and have identified an essential role in spermatogenesis. Conditional knockout (cKO) of Rheb in the male germline resulted in severe oligoasthenoteratozoospermia and male sterility. More detailed phenotypic analyses uncovered an age-dependent meiotic progression defect combined with subsequent abnormalities in spermiogenesis as evidenced by abnormal sperm morphology. In the female, however, germ-cell specific inactivation of Rheb was not associated with any discernible abnormality; these cKO mice were fertile with morphologically unremarkable ovaries, normal primordial follicle formation, and subsequent follicle maturation. The absence of an abnormal ovarian phenotype is striking given previous studies demonstrating a critical role for the mTORC1 pathway in the maintenance of primordial follicle pool. In conclusion, our findings demonstrate an essential role of Rheb in diverse aspects of spermatogenesis but suggest the existence of functionally-redundant factors that can compensate for Rheb deficiency within oocytes.