Cell and Developmental Biology University of Michigan

Research

Chromosome dynamics required for successful meiosis, in particular, for meiotic homologous pairing.

In sexually reproducing organisms, diploid germ cells produce haploid gametes (egg and sperm) by a specialized cell division process known as meiosis. During meiosis, chromosomes are segregated at two successive divisions without intervening DNA replication, reducing ploidy by half. In meiotic prophase, maternally and paternally-derived homologous chromosomes engage in crossover recombination events, resulting both in exchange of genetic material and formation of chiasmata that physically connect the homologs and ensure their segregation to opposite spindle poles at the first meiotic division. Prior to successful recombination, each chromosome locates, recognizes and associates with its homologous partner (homologous pairing) and then this association is stabilized by protein structure (synapsis). A failure in any of these steps can lead to chromosome rearrangement and/or non-disjunction, a leading cause of birth defects and miscarriages.

Our laboratory is focusing on studying the chromosome dynamics required for successful meiosis, in particular, for meiotic homologous pairing. Although this process is essential for sexual reproduction, we are only beginning to understand its molecular mechanisms and many basic questions remain to be answered. How do chromosome move around in a nucleus in search for their homologous partner? How do chromosomes recognize their homology? How do chromosomes keep homologous association and/or discourage non-homologous association? How are initial association and stabilization (synapsis) coordinated? To address these fundamental questions, we use a simple model organism: the nematode C. elegans and employ a wide variety of techniques including functional genomics, genetics, molecular biology, cell biology and high-resolution 3-D microscopy.

Lab Members

• Nicholas Stefanski
  Research Lab Technician
• Ajit Ramadugu
  Undergradate Student

Publications

1. Nabeshima, K. Collaborative Homologous Pairing during C. elegans Meiosis. Worm 2012, accepted.
2. Dombecki, C.R., Chiang, A.C.Y., Kang, H.-J., Bilgir, C., Stefanski, N.A., Neva, B.J., Klerkx, E.P.F., and Nabeshima, K. The Chromodomain Protein MRG-1 Facilitates SC-Independent Homologous Pairing during Meiosis in Caenorhabditis elegans. Developmental cell 2011, 21, 1092-1103.
3. Nabeshima, K., Mlynarczyk-Evans, S., and Villeneuve, A. M. Chromosome Painting Reveals Asynaptic Full Alignment of Homologs and HIM-8 Dependent Remodeling of X Chromosome Territories during Caenorhabditis elegans Meiosis. PLoS genetics 2011, 7, e1002231.
4. Henzel, J. V.,Nabeshima, K., Schvarzstein, M., Turner, B. E., Villeneuve, A. M., and Hillers, K. J. An Asymmetric Chromosome Pair Undergoes Synaptic Adjustment and Crossover Redistribution During Caenorhabditis elegans Meiosis: Implications for Sex Chromosome Evolution. Genetics 2011, 187, 685-699.
5. Nabeshima, K. Chromosome Structure and Homologous Chromosome Association During Meiotic Prophase in Caenorhabditis elegans. Methods Mol Biol 2011, 549-562.
6. Yuen, K.W., Nabeshima, K., Oegema, K., and Desai, A. Rapid De Novo Centromere Formation Occurs Independently of Heterochromatin Protein 1 in C. elegans Embryos. Curr Biol 2011, 21, 1800-1807.
7. Nabeshima, K., Villeneuve, A. M., and Colaiacovo, M. P. Crossing over is coupled to late meiotic prophase bivalent differentiation through asymmetric disassembly of the SC. J Cell Biol 2005, 168, 683-689.
8. Nabeshima, K., Villeneuve, A. M., and Hillers, K. J. Chromosome-wide regulation of meiotic crossover formation in Caenorhabditis elegans requires properly assembled chromosome axes. Genetics 2004, 168, 1275-1292.
9. Couteau, F., Nabeshima, K., Villeneuve, A., and Zetka, M. A component of C. elegans meiotic chromosome axes at the interface of homolog alignment, synapsis, nuclear reorganization, and recombination. Curr Biol 2004, 14, 585-592.
10. Shimada M., Nabeshima K., Tougan T., and H. Nojima. The meiotic recombination checkpoint is regulated by checkpoint rad+ genes in fission yeast. EMBO J 2002, 21: 2807-2818, 2002.
11. Nabeshima, K., Y. Kakihara, Y. Hiraoka, and H. Nojima. A novel meiosis-specific protein of fission yeast, Meu13p, promotes homologous pairing independently of homologous recombination. EMBO J 2001, 20: 3871-3881.