Completed Genetics & Molecular Biology Cells, Biochemistry & Physiology

The specialised apparatus for meiotic chromosome segregation in oocytes.

Funder Wellcome Charity-funded
Recipient organisation University of Edinburgh
Funding £1.5M
Period Dec 2012 — Nov 2018

In plain English

AI plain-English summary

Human eggs build a chromosome-separating machine that works nothing like the one in ordinary cells, and scientists want to know how it is put together. This matters because human eggs frequently make errors when dividing their chromosomes—far more often than sperm or body cells do. Those errors cause miscarriages and genetic conditions like Down syndrome. The problem is that researchers cannot experiment on human eggs, so the molecular reasons for this fragility remain unknown. This project uses fruit fly eggs, which share the same unusual chromosome-separation features as human eggs, to uncover the underlying mechanisms. The research is fundamental science. It will not produce a medical test or treatment in the short term. But understanding how a normal egg builds its chromosome-separation apparatus is a necessary first step toward explaining why it so often fails. Past discoveries about how cells divide have led to cancer drugs and fertility treatments. A deeper grasp of egg-specific chromosome segregation could eventually help predict or prevent age-related infertility and chromosomal disorders.

View original technical description
To segregate meiotic chromosomes, oocytes form a specialised apparatus distinct from mitosis or male meiosis. These key distinct features stem from the unique organisation of meiotic chromosomes and the spindle, and the specialised mode of their interaction. Understanding these underlying mechanisms could reveal why human oocytes mis-segregate chromosomes so frequently, but little is known about their molecular basis. Although experimentation on human oocytes is virtually impossible, cruciall y these features are common in Drosophila and mammalian oocytes. Therefore we use the Drosophila oocyte as a model system, because it is ideal for gene discovery and detailed mechanistic analysis. Our ultimate goal is to find out how oocytes set up a specialised chromosome segregation apparatus. More specifically, we will uncover the molecular basis of three crucial features specialised to oocytes: 1) clustering of meiotic chromosomes away from the nuclear envelope in the prophase nucleus, 2 ) spindle assembly in the absence of centrosomes, 3) prominence of a kinetochore-independent pathway to align chromosomes. Our findings in Drosophila oocytes will provide unique insights into chromosome segregation and mis-segregation in human oocytes.

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Researchers

Hiroyuki Ohkura (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Assembly of the meiotic spindle in the large oocyte volume
Dissecting actin-dependent chromosome cohesion in mammalian oocytes
Specialization of chromosome segregation mechanisms in meiosis
Setting up the spindle in the mammalian egg for meiosis and embryo development
The role of the kinetochore in meiotic aneuploidy

Original classification

Senior Research Fellowship Basic Renewal

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.