Co-workers:

Accurate segregation of genetic materials is essential for life. A failure or error in this process could result in cell death or aneuploidy which is thought to be a contributing factor in the development of cancer. A bipolar spindle is formed during cell division to mediate chromosome segregation in eukaryotes. Centrosomes dictate spindle formation during mitosis, while a bipolar spindle forms without centrosomes in female meiosis. Chromosomesegregation in female meiosis is error prone in humans, and mis-segregation is a major cause of infertility, miscarriages, and birth defects. In spite of its importance for human health and the understanding of basic cellular function, little is know about the molecular mechanism of the spindle formation in female meiosis in vivo.

To understand the molecular basis of meiotic division in oocytes, we have isolated a number of Drosophila mutants which are defective in various aspects of spindle formation or chromosome alignment in oocytes. Analysis of these mutants has revealed the crucial role of the meiotic chromosome organisation in the formation of the spindle in female meiosis. Furthermore, our study has identified conserved protein kinases and microtubule regulators, and highlighted meiosisspecific adaptation which compensates for a lack of centrosomal activity.

A spindle is made of highly organised arrays of microtubules. Microtubules constitute a major cytoskeletal system in eukaryotic cells and regulate a diverse set of processes during development, such as cell polarity, intracellular transport and cell motility. The organisation and dynamics of microtubules changes dramatically during the cell cycle and development. Mis-regulation of microtubules is associated with many diseases. We aim to understand the molecular regulation of microtubules in the context of cell division and development using a multi-disciplinary approach. Microtubule-associated proteins (MAPs) and microtubule motors are thought to play crucial roles in microtubule regulation. Using Drosophila as a model system, we have revealed how conserved and non-conserved MAPs regulate microtubule organisation and dynamics in dividing and non-dividing cells.

Selected publications:

 
Lancaster, O. M., Breuer, M., Cullen, C. F., Ito, T., and Ohkura, H. (2010). The meiotic recombination checkpoint suppresses NHK-1 kinase to prevent reorganisation of the oocyte nucleus in Drosophila. PLoS Genet 6, e1001179.
Meireles, A. M., Fisher, K. H., Colombié, N., Wakefield, J. G., and Ohkura, H. (2009). Wac: a new Augmin subunit required for chromosome alignment but not for acentrosomal microtubule assembly in female meiosis. J. Cell. Biol. 184, 777-784.
Colombie, N., Cullen, C. F., Brittle, A. L., Jang, J. K., Earnshaw, W. C., Carmena, M., McKim, K., and Ohkura, H. (2008). Dual roles of Incenp crucial to the assembly of the acentrosomal metaphase spindle in female meiosis. Development 135, 3239- 3246.