Errors in chromosome segregation in meiosis lead to incorrect numbers of chromosomes in the resulting gamete. The most common tolerated aneuploidy is trisomy 21, commonly known as Down Syndrome, which leads to a significant increase in the incidence of congenital heart disease. Oocyte meiosis, the formation of haploid gametes through two rounds of reductional cell division in females, results in over 95% of all detectable errors in human meiosis. In most organisms including humans, the error-prone oocyte meiotic spindle lacks centrosomes (is acentrosomal) and therefore the molecular mechanisms underlying spindle assembly and faithful chromosome segregation are poorly understood. In this study, we propose to use the model organism C. elegans to probe the molecular forces fundamental to proper acentrosomal spindle assembly and maintenance in an effort to understand the structural basis of aneuploidy. We hypothesize that an essential plus-end directed molecular motor kinesin-12/KLP-18, in concert with a required adaptor protein MESP-1, generates an outward force on spindle microtubules that is required for the acentrosomal spindle to achieve and maintain bipolarity.
|Effective start/end date||1/1/17 → 12/31/18|
- American Heart Association Midwest Affiliate (17PRE33440016)