Completed Genetics & Molecular Biology Cells, Biochemistry & Physiology

Chromosome segregation in mammalian meiosis

In plain English

AI plain-English summary

Every human egg must hold its chromosomes together with protein rings for decades, from before birth until ovulation. This research investigates how those rings stay intact for so long—and why they sometimes fail. When chromosome rings break too early, eggs end up with the wrong number of chromosomes. That can cause miscarriages or conditions like Down’s syndrome. The problem becomes more common as women age, and the underlying mechanism is not understood. This project aims to fill that gap by watching, in real time, how mutant mouse eggs with fluorescently labelled chromosomes divide. By removing specific proteins known to control chromosome segregation in other organisms, the researchers can see exactly which steps go wrong. They will also study infertile mutant animals to find entirely new regulators of the process. This is fundamental science. It will not produce a treatment or diagnostic test in the short term. But understanding why chromosome rings degrade over decades could eventually explain why fertility declines with age and point toward ways to preserve egg quality. Similar fundamental work on chromosome mechanics has already shaped how we think about cancer cell division and genetic disorders.

View original technical description
We are trying to identify mechanisms that ensure each egg receives a single copy of every chromosome. The inheritance of too many or too few chromosomes can result in spontaneous miscarriages or severe birth defects as in Down’s Syndrome or trisomy of chromosome 21. We know that cells in the body regulate the equal distribution of chromosomes by entrapping sister chromosomes within protein rings. These rings are only destroyed when cells are ready to divide. In women, the rings must hold together sister chromosomes in eggs from birth until fertilization, which can be separated by decades. We are investigating how these rings are stably maintained. Loss of rings over time could be responsible for maternal age-related infertility. We are using animal models to study chromosome segregation in eggs with the aim to understand the equivalent processes in humans. We are studying eggs lacking specific proteins that are known to be important for chromosome segregation in other organisms. We are taking movies of mutant eggs carrying fluorescently labelled chromosomes to identify which aspects of chromosome segregation are defective due to loss of a particular protein. We also hope to identify new regulators of the egg divisions by studying infertile mutants.

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Researchers

Kikue Tachibana-Konwalski (Co-Investigator)Kim Nasmyth (Principal Investigator)

Related Research

Grants with similar aims, by meaning.

Chromosome Cohesion during Protracted Meiotic Arrest in Oocytes
Maintaining Genetic and Chromosomal Stability in the Mammalian Germline
Regulation of oocyte cohesin and chromosome segregation defects in the female germ line
The role of spindle dynamics in segregating chromosomes in mammalian oocytes and embryos
Mechanism and regulation of chromosome replication

Original classification

Research Grant

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