Investigation of meiotic organelle checkpoint functions by Drosophila Myt1

  • Author / Creator
    Varadarajan, Ramya
  • Meiosis in eukaryotes includes a developmentally programmed pre-meiotic G2 phase arrest before the onset of MI division mediated by inhibitory phosphorylation of Cdk1. There are two inhibitory kinases, Wee1 and Myt1. Myt1 mediated Cyclin B-Cdk1 regulation serves as a conserved mechanism for maintaining pre-meiotic oocyte arrest in many animal models. Earlier reports from the Campbell lab, however, have shown that loss of Myt1 activity affected multiple aspects of Drosophila spermatogenesis resulting in male sterility. The conserved meiotic checkpoint function of Myt1 was hypothesized to account for myt1 mutant male sterility, as Drosophila spermatocytes normally undergo a developmentally regulated premeiotic G2 phase arrest before MI. This possibility, however, has not been tested. Here I show that loss of Myt1 activity neither affects the timing of pre-meiotic G2 phase arrest nor the overall coordination of G2/MI transition. Instead, the phenotypic analysis of myt1 mutants indicated that Myt1 activity is required for structural integrity of a germline specific membranous cytoskeletal organelle called the fusome (or intercellular bridges). I found that inhibition of Cyclin A-Cdk1 during early spermatocyte development requires Myt1activity to prevent fusomes from premature Cdk1 activation. Mis-regulation of Cyclin A-Cdk1 during spermatocyte development also perturbed premature centrioles dis-engagement, producing multipolar meiotic spindles resulting in aneuploidy of myt1 meiocytes. I conclude that the role of Myt1 during pre-meiotic G2 phase arrest of male meiosis is to regulate discrete checkpoint mechanisms that are used to spatially and temporally coordinate cytoplasmic organelle behavior with the nuclear events of meiotic progression that are triggered by Cdc25Twe-mediated Cdk1 activation, at G2/MI.

  • Subjects / Keywords
  • Graduation date
    Spring 2016
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
  • Specialization
    • Molecular Biology and Genetics
  • Supervisor / co-supervisor and their department(s)
  • Examining committee members and their departments
    • Hughes, Sarah (Department of medical genetics)
    • Chan, Gordon (Department of Oncology)
    • Srayko, Martin (Biological sciences)