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Investigating the role of CRL5, an ubiquitin ligase, in ovarian follicle development.

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Date

2016-07-20

Authors

Hardy, Victoria L

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Publisher

East Carolina University

Abstract

During oogenesis, follicle cells surround maturing oocytes, which produce factors necessary for proper oocyte growth and development. Correct encapsulation of the oocyte by follicle cells is therefore essential for reproduction. While many signaling pathways have been linked to encapsulation, mechanisms of early follicle development, particularly in mammals, are not fully understood. Recent evidence demonstrates that Cullin-RING E3 ubiquitin ligases (CRLs) are necessary for oogenesis in both mammals and Drosophila. CRLs include a Cullin family scaffolding protein and a RING-domain protein that facilitates recruitment of ubiquitin ligases. CRLs are known to control many cellular processes; however, it is unclear how CRLs control early follicle development. In Drosophila, loss of Cul5, results in follicle death and improper encapsulation. We therefore tested whether the Cul5-containing CRL (CRL5) is required for early follicle development by analyzing loss-of-function mutants of the ligase complex. Loss of Cul5 or the RING protein Roc2 resulted in fused follicles, ruptured follicular epithelium, and improper encapsulation. The encapsulation phenotypes are not due to an over proliferation of germ cell; in fact, Cul5 mutants display a disturbance of the cell cycle which causes a decrease in germline stem cell proliferation. Genetic mosaics of Cul5 or Roc2 show that CRL5 is primarily required in developing follicle cells for cyst encapsulation. CRL5 mutant follicle cells display mislocalization of the polarity protein Bazooka and decreased Stat expression. Data also suggest that Cul5 may mediate signaling between the follicle cells and the underlying cyst. Results suggest that CRL5 controls early follicle development by regulating early follicle cell polarity and specification. Our studies highlight the role of CRLs in early follicle development, and may lead towards a better understanding of the cellular and mechanical processes that control follicle formation.

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