The overall goal of this proposal is to determine the role of the dual-specificity phosphatase Cdc14 during mammalian meiosis. Meiosis is the process by which a diploid precursor cell produces haploids and it is linked to species-specific differentiation programs that generate gametes. Cdc14 is highly conserved throughout evolution and is a critical mitotic cell-cycle regulator in all organisms studied to date. In budding yeast, Cdc14 mutants are unable to properly complete the first meiotic division where homologs are segregated. Mistakes in meiosis I are linked to nondisjunctions and chromosomal anomalies in humans. Higher eukaryotes contain 2 Cdc14 proteins, Cdc14a and Cdc14b, and the functions of both will be explored in this proposal.
The specific aims of this proposal are to 1) test the hypothesis that Cdc14a and Cdc14b are required for meiosis in the mouse oocyte using an RNA interference (RNAi) approach, 2) test the hypothesis that over-expression of Cdc14a and Cdc14b will alter meiosis in the mouse oocyte and develop a method to image living oocytes and 3) identify domains within the CDC14 proteins that regulate their subcellular localization during meiosis by mutagenesis. Meiosis is the process that generates eggs in females and sperm in males. Female meiosis is highly error- prone in humans as approximately 20% of all eggs contain abnormal chromosome numbers that, when fertilized by sperm, leads to spontaneous abortions, stillbirths and, in live births, developmental diseases like Down Syndrome. Exploring how the meiotic cell cycle is regulated is key to gaining an understanding of how errors in the segregation of DNA are linked to human chromosomal disorders. ? ? ?

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Postdoctoral Individual National Research Service Award (F32)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-F06-G (20))
Program Officer
Tasca, Richard J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pennsylvania
Schools of Arts and Sciences
United States
Zip Code
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 :
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
Shuda, Kristy; Schindler, Karen; Ma, Jun et al. (2009) Aurora kinase B modulates chromosome alignment in mouse oocytes. Mol Reprod Dev 76:1094-105
Buffone, Mariano G; Schindler, Karen; Schultz, Richard M (2009) Overexpression of CDC14B causes mitotic arrest and inhibits zygotic genome activation in mouse preimplantation embryos. Cell Cycle 8:3904-13
Schindler, Karen; Schultz, Richard M (2009) CDC14B acts through FZR1 (CDH1) to prevent meiotic maturation of mouse oocytes. Biol Reprod 80:795-803
Schindler, Karen; Schultz, Richard M (2009) The CDC14A phosphatase regulates oocyte maturation in mouse. Cell Cycle 8:1090-8