Regulators of the Drosophila oocyte-to-embryo transition

Abstract

The transition from oocyte to embryo is critical across metazoans, as it marks the onset of development and is essential for fertility. Although many important regulators of the oocyte-to-embryo transition have been uncovered, our understanding of how their activities are controlled is limited. Moreover, there are likely to be additional regulators as yet unidentified. This thesis describes investigation into new and known regulators of the oocyte-to-embryo transition in Drosophila. Control of mRNA translation is a crucial part of egg activation, the trigger for the oocyte-to-embryo transition. The PNG kinase is a master regulator of mRNA translation at egg activation in Drosophila. The activity of PNG is coupled with the completion of the meiotic cell cycle by regulated binding of the GNU activating subunit. The protein interactions and localization of the GNU regulatory subunit in mature oocytes were analyzed, revealing an unexpected link between GNU and RNP granules.

The functional roles of the domains of GNU were defined. Delineating developmental control of the PNG kinase complex is key to understand fully the changes in the translational landscape at the oocyte-to-embryo transition. Changes in mRNA translation are accompanied by changes in protein levels during the oocyte-to-embryo transition. Many proteins change in a manner that suggest developmental regulation, and thus are potential new regulators of the oocyte-to-embryo transition in Drosophila. A targeted screen of genes encoding proteins that appear to be under developmental regulation at this time was performed. Several genes were identified that are required for the proper onset of embryogenesis. Two of these genes, CG5003, a putative SCF subunit, and nebulosa (CG10960), a putative sugar transporter, were characterized. Elucidating the mechanisms through which these genes ensure the oocyte-to-embryo transition will yield fundamental insights.

These findings add new understanding to the regulation underlying the oocyte-to-embryo transition in Drosophila, painting a more complex picture than previously appreciated. They reveal the myriad of processes whose proper developmental control and execution is crucial for fertility.