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Hiro Ohkura

Co-workers:

Robin Beaven, Sophie Bourbon, Manuel Breuer, Mariana Costa, Fiona Cullen, Pierre Romé, Liudmila Zhaunova
Ohkura Lab Website

Meiotic cell division and microtubule regulation

Hiro gives a brief overview of his research.

Accurate segregation of chromosomal DNA is essential for life. A failure or error in this process during somatic divisions could result in cell death or aneuploidy. Furthermore, chromosome segregation in oocytes is error prone in humans, and mis-segregation is a major cause of infertility, miscarriages and birth defects. The chromosome segregation machinery in oocytes shares many similarities with these in somatic divisions, but also has notable differences. In spite of its importance for human health, little is known about the molecular pathways which set up the chromosome segregation machinery in oocytes. Defining these molecular pathways is crucial to understand error-prone chromosome segregation in human oocytes. Furthermore, evidence indicates that these apparent oocyte-specific pathways also operate in mitosis, although less prominently, to ensure the accuracy of chromosome segregation. Therefore uncovering the molecular basis of these pathways is also important to understand how somatic cells avoid chromosome instability, a contributing factor for cancer development.

To understand the molecular pathways which set up the chromosome segregation machinery in oocytes, we take advantage of Drosophila oocytes as a “discovery platform” because of their similarity to mammalian oocytes and suitability to a genetics-led mechanistic analysis. In Drosophila oocytes, like in human oocytes, meiotic chromosomes form a compact cluster called the karyosome within the nucleus. Later, meiotic chromosomes assemble the spindle without centrosomes, establish bipolar attachment and congress within the spindle. We have identified a number of genes defective in chromosome organisation and/or spindle formation in oocytes.

From the study of the karyosome, we found that the nuclear pore plays a major role in global chromatin organisation in oocytes and somatic cells, and identified a novel regulatory system within the pore which controls the chromatin attachment state to the nuclear envelope. Furthermore, we identified that the NuRD nucleosome remodelling complex has a crucial role in chromosome condensation. We also showed that microtubule plus ends are actively prevented from forming stable attachments to kinetochores during spindle formation in Drosophila oocytes. The microtubule catastrophe-promoting complex Sentin-EB1 is responsible for this delay in attachment, and facilitates bipolar attachmentof homologous chromosomes. To understand differences in the modes of microtubuleattachment to kinetochores in oocytes and mitotic cells, we built a universal mathematical model that is applicable to eukaryotic cell divisions in general and that explains theobserved differences between mitosis and meiosis.

Selected publications:

A. The meiotic chromosomes (arrows) cluster away from the nuclear envelope in wild-type oocytes, but are closelyassociated with the nuclear envelope of Nup62 mutant oocytes.
B. Loss of Nup62 disrupts global chromatin organisation in somatic cell lines, which is rescued by co-depletion of Nup155.
C. Model for the chromatin attachment state controlled by an internal regulatory circuit in the NPC.


A. The meiotic chromosomes (arrows) cluster away from the nuclear envelope in wild-type oocytes, but are closely associated with the nuclear envelope of Nup62 mutant oocytes.
B. Loss of Nup62 disrupts global chromatin organisation in somatic cell lines, which is rescued by co-depletion of Nup155.
C. Model for the chromatin attachment state controlled by an internal regulatory circuit in the NPC.