Date of Award

2013

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Biological Sciences

First Advisor

Swan, Andrew

Keywords

Biological sciences, Health and environmental sciences, Anaphase promoting complex, Chromosome segregation, Meiosis, Sex determination, Spindle assembly checkpoint

Rights

CC BY-NC-ND 4.0

Abstract

Meiosis is an important biological process that results in the formation of 4 haploid gametes. It is a modified cell division that involves two rounds of chromosome segregation without intervening DNA replication. Meiosis stages are driven by cell cycle regulators that, to a large degree, are shared with mitosis. We studied the role and the regulation of the cell cycle regulator, the Anaphase Promoting Complex/Cyclosome (APC/C) in Drosophila female meiosis. We first investigated the role of the Spindle Assembly Checkpoint (SAC), a known inhibitor of APC/C activity in mitosis, in controlling APC/C activity during meiosis. We find that the loss of SAC does not affect the overall Cyclin B levels in the egg or the local accumulation of Cyclin B on the meiotic spindles, as we would expect based on the known role of SAC in inhibiting APC/C activity in mitosis. Furthermore, the loss of SAC does not affect the segregation of either the homologous chromosomes at meiosis I, or the sister chromatids at meiosis II. The segregation of sister chromatids in mitosis depends on the APC/C-mediated degradation of the Separase inhibitor, Securin, which relieves the inhibition on Separase allowing sister chromatid segregation. We studied the significance of Securin degradation in meiosis. We find that while stabilization of Securin causes a delay in meiosis, it does not prevent the segregation of either the homologous chromosomes at meiosis I or the sister chromatids at meiosis II. In contrast to the weak effect on meiosis, stabilization of Securin causes an early mitotic arrest in the embryo. Finally, we investigated the significance of the restricted expression of Cort, a Drosophila female-specific APC/C activator, in the germline. We find that the misexpression of Cort outside the germline leads, surprisingly, to sex transformation of females toward the male fate. This led us to uncover an important role of maternal Cort in promoting male sexual development, possibly by inhibiting the activity of Tra/Tra2 splicing complex.

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