| dc.description.abstract | CELL AND DEVELOPMENTAL BIOLOGY
THE ROLE OF α-ENDOSULFINE IN THE
FEMALE MEIOTIC CELL CYCLE IN DROSOPHILA
JESSICA R. VON STETINA
Dissertation under the direction of Professor Daniela Drummond-Barbosa
Meiosis is coupled to gamete development and must be well regulated to prevent chromosomal abnormalities such as aneuploidy. During meiotic maturation, Drosophila oocytes progress from prophase I to metaphase I. The molecular factors controlling meiotic maturation timing, however, are poorly understood. My work in this thesis shows that Drosophila α-endosulfine (endos) plays a key role in this process. endos mutant oocytes have a prolonged prophase I arrest and fail to progress to metaphase I. This phenotype is similar to that of mutants of cdk1 and of twine, the meiotic homolog of cdc25, which is required for Cdk1 activation. I found that Twine and Polo kinase levels are reduced in endos mutants and identified Early girl (Elgi), a predicted E3 ubiquitin ligase, as a strong Endos-binding protein. In elgi mutant oocytes the transition into metaphase I occurs prematurely, but Polo and Twine levels are unaffected. These results suggest that Endos controls meiotic maturation by regulating Twine and Polo levels and, independently, by antagonizing Elgi. Interestingly, I also found that endos genetically interacts with Matrimony (Mtrm), which is a negative regulator of polo required to set the timing of meiotic maturation and the proper orientation of chromosomes. endos dominantly rescues the premature nuclear envelope breakdown defects observed in mtrm heterozygous females but enhances their chromosome misorientation defects, demonstrating that these processes are independent from each other. It is possible that the genetic interactions between endos and Mtrm occur via their effects on Polo, but other mechanisms are also conceivable. Finally, germline-specific expression of the human α-endosulfine ENSA rescues the endos meiotic defects and infertility, and α-endosulfine is expressed in mouse oocytes, suggesting potential conservation of its meiotic functions.
Approved: Daniela Drummond-Barbosa | |
