Assembly of the meiotic spindle in the large oocyte volume

Chromosome mis-segregation is frequent in human meiotic oocytes and a major cause of infertility, miscarriage and congenital conditions, such as Down syndrome. Chromosome segregation is mediated by a spindle made of bipolar microtubule arrays. Spindle assembly in oocyte meiosis is challenging, as it is done in the exceptionally large oocyte volume and without centrosomes, the main microtubule-organising centres in mitosis. Despite the potential medical significance, spindle assembly in oocytes is less well understood at the molecular level than in mitosis, due to technical difficulties. To overcome these difficulties, we use Drosophila oocytes as a "discovery platform" that can uniquely combine genetic, cytological and biochemical approaches. The key goal of this proposal is to address the following fundamental unanswered questions at the molecular level, based on our new innovative methods and unpublished findings. 1.How do chromosomes locally activate spindle assembly in the large oocyte? 2.What is the role of spindle envelope/matrix which embeds the spindle in oocytes? 3.How do proteins co-operatively assemble the stable bipolar spindle in oocytes? Answering these long-standing questions will reveal how the bipolar stable spindle is assembled without centrosomes in the large oocytes. It could potentially provide unique insights into frequent chromosome mis-segregation in human oocytes.