Haploid gametes, that are essential for sexual reproduction, are generated fronn diploid precursor cells via meiosis. In females, oocytes undergo 2 major meiosis-specific, cell-cycle transitions wtiose regulation are poorly understood. Thie first transition is meiotic resumption where oocytes exit a prolonged prophase arrest and enter the first meiotic M phase (Ml), and the second is the transition between Ml and Mil where homologous chromosomes separate and no round of DNA synthesis occurs. This project began while the PI (Karen Schindler) was a postdoctoral fellow at the University of Pennsylvania and has facilitated transition to an independent research career. These studies investigating the molecular mechanisms that lead to aneuploidy in female eggs will form the basis of an independent research program in the Department of Genetics at Rutgers, The State University of New Jersey where the PI will assume a tenure-track faculty position in January 2012. The environment at Rutgers for research in reproductive biology and aneuploidy is outstanding, all resources required to complete the studies are available, and the institution is committed to promoting development of new investigators. Thus, the PI will be well-positioned to compete for additional funding and to have a successful independent research career.
Meiosis is the process that generates eggs and sperm required for sexual reproduction. Female meiosis is highly error-prone in humans;-20% of all eggs contain abnormal chromosome numbers (aneuploidy) that are linked to spontaneous abortions, stillbirths and developmental diseases like Down Syndrome. The major goal of this proposal is to determine the mechanism(s) that lead to aneuploidy in eggs using the mouse model.
|Balboula, Ahmed Z; Nguyen, Alexandra L; Gentilello, Amanda S et al. (2016) Haspin kinase regulates microtubule-organizing center clustering and stability through Aurora kinase C in mouse oocytes. J Cell Sci 129:3648-3660|
|Balboula, Ahmed Z; Stein, Paula; Schultz, Richard M et al. (2015) RBBP4 regulates histone deacetylation and bipolar spindle assembly during oocyte maturation in the mouse. Biol Reprod 92:105|
|Balboula, Ahmed Z; Schindler, Karen (2014) Selective disruption of aurora C kinase reveals distinct functions from aurora B kinase during meiosis in mouse oocytes. PLoS Genet 10:e1004194|
|Nguyen, Alexandra L; Gentilello, Amanda S; Balboula, Ahmed Z et al. (2014) Phosphorylation of threonine 3 on histone H3 by haspin kinase is required for meiosis I in mouse oocytes. J Cell Sci 127:5066-78|
|Oh, Jeong Su; Susor, Andrej; Schindler, Karen et al. (2013) Cdc25A activity is required for the metaphase II arrest in mouse oocytes. J Cell Sci 126:1081-5|
|Schindler, Karen; Davydenko, Olga; Fram, Brianna et al. (2012) Maternally recruited Aurora C kinase is more stable than Aurora B to support mouse oocyte maturation and early development. Proc Natl Acad Sci U S A 109:E2215-22|
|Stein, Paula; Schindler, Karen (2011) Mouse oocyte microinjection, maturation and ploidy assessment. J Vis Exp :|
|Schindler, Karen (2011) Protein kinases and protein phosphatases that regulate meiotic maturation in mouse oocytes. Results Probl Cell Differ 53:309-41|
|Chiang, Teresa; Duncan, Francesca E; Schindler, Karen et al. (2010) Evidence that weakened centromere cohesion is a leading cause of age-related aneuploidy in oocytes. Curr Biol 20:1522-8|