减数分裂I期纺锤体动力学的分子调控机制

减数分裂将单次复制的DNA遗传物质经连续的两次细胞分裂分配形成单倍体配子，进而确保后续生殖发育过程细胞染色体数目的稳定。纺锤体通过微管与染色体上的动点连接，介导染色体的准确分配。减数分裂I期姐妹染色体上的动点形成单极定向而非有丝分裂的双极定向，同时同源染色体发生交叉。这些特异的结构使减数分裂I期纺锤体动力学亦发生相应变化，其过程可能由特异的分子机制调控。人们对减数分裂I期纺锤体动力学调控的研究仍然不多、理解不足。我们初步的研究不仅揭示了减数分裂I期纺锤体延伸较快、达到中期的长度更长等特点，而且鉴定出了调控减数分裂I期纺锤体动力学的特异驱动蛋白klp2p。因此，我们拟综合利用高分辨荧光活细胞显微镜观察技术，酵母遗传学及生物化学手段，系统研究减数分裂I期纺锤体动力学的分子调控机理。由于减数分裂与生殖健康紧密相关，因此本研究将为生殖医学研究奠定坚实的理论基础。

During meiosis, DNA duplicates once and is segregated into gametes through two consecutive cell divisions. This makes the gametes become haploid and allows fertilized cells to return to a diploid state. The spindle is responsible for chromosome segregation with its microtubules attached to the kinetochores on the chromosomes. Unlike mitotic kinetochores which are organized in a bi-orientation configuration, kinetochores on the sister chromosomes are mono-oriented during meiosis I, while homologous chromosomes pair and form chiasmata. Mono-oriented sister kinetochores and chiasmata may then contribute to the unique spindle dynamics as discovered in our recent preliminary study. Intriguingly, the meiotic spindle appears to elongate faster and reach a longer metaphase length than the mitotic spindle during preanaphase I . In addition, we have identified the minus –end directed kinesin klp2p as a key player in regulating meiotic spindle dynamics. Based on this preliminary data, we proposed that meiotic I spindle dynamics may be regulated by yet unknown mechanisms involved klp2p and/or other key spindle regulatory proteins such as ase1p and cut7p. In this proposal, we will employ a combination of live-cell microscopy, yeast genetics and biochemical approaches to uncover the molecular mechanisms underlying meiotic spindle dynamics. As meiosis is essential for sexual reproduction, our work will facilitate the further development of reproductive biology.