Meiosis

Meiosis is an integral step in the eukaryotic life cycle. During the two rounds of meiotic division the genetic complement of a diploid cell is reduced by half to form haploid gametes. Defects in this process can lead to chromosomal abnormalities and cause birth defects in humans.

Meiosis

Process of meiosis. In meiosis, the diploid cell first undergoes DNA replication so that each chromosome consists of sister chromatids (two lines). Pairing and recombination of homologous chromosomes (big or small) then occurs. The two meiotic divisions are known as meiosis I and meiosis II. While homologous chromosomes are separated in meiosis I, sister chromatids are separated in meiosis II.

Prophase I is the stage of meiosis when pairing (synapsis) of homologous chromosomes occurs and DNA is exchanged in homologous recombination. Prophase I is comprised of a series of substages that are distinct with respect to chromosome appearance (see figure). Given that prophase I is when the important processes of meiosis occur, this is where our research is focussed.

Meiotic prophase. In leptotene, the nucleus consists of individual strands of replicated chromosomes (the two lines). In zygotene, synapsis of homologous chromosomes (red and blue) takes place through assemply of the synaptonemal complex and the telomeres of the chromosomes cluster to form a ‘bouquet’ structure. In pachytene, the chromosomes are condensed and cross over of DNA can occur. In diplotene, the synaptonemal complex is degraded and the chiasmata resulting from crossing over become visible.

Understanding the mechanisms underlying the dynamic chromosomal events of meiosis can help us to understand how genomes are passed from one generation to the next.

Model organisms

Yeast

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The brewer’s yeast, Saccharomyces cerevisiae, is a well established model of eukaryotic genetics. One of the advantages of using S. cerevisiae to study meiosis is that the cells can be grown stably as either diploids or haploids. To initiate meiosis, the yeast is simply transferred to a nutrient restricted media that induces sporulation. We have developed a system to track the proximity of chromosomal loci in 3D over time (4D) throughout meiosis to track the pairing dynamics of homologous chromosomes. To study the role that different genes play in meiosis we are able to use the yeast knockout collection or alter the genes ourselves using homologous recombination.

Zebrafish

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The zebrafish, Danio rerio, is an increasingly popular model of vertebrate development. Using this model, we are able to study the sexually dimorphic aspects of meiosis in male and female fish. Zebrafish development is very accessible, gametogenesis occurs throughout adulthood in both the sexes and the embryos produced by mating develop outside of the body. We have developed a collection of tools in zebrafish to visualize the chromosome events that occur during meiosis and we can relate these to offspring development.

The 4D prophase nucleus

Model

Chromosome dynamics during pairing. Forces influence both homologs. Actin-based associations are shown at telomeres (green) and at interstitial sites (blue). Arrows around the periphery of the nucleus indicate direction of movement for the telomeres (green) and the interstitial sites (blue). Grey arrows in the interior of the nucleus show “Brownian-like” motion/unknown forces on the chromosomes.

The research in our lab is aimed at addressing how chromosomes achieve their dynamic motion and reorganisation during prophase I of meiosis. Our hypothesis is that the chromosomal changes in space and time are governed by the nuclear context.

The female meiotic nucleus is larger than that of the male and this must impact on the mechanics of meiosis. While female meiosis in mammals occurs inside the fetal ovary, female meiosis in fish occurs throughout adulthood; this allows us to compare the sexually dimorphic aspects of meiosis in a way not possible in other models. In both sexes, double strand breaks form throughout the nucleus and then coalesce into a focussed region near the telomere bouquet. How are the events of meiotic prophase conserved between males and females when the nuclear landscape is so different?

When a chromosome is pulled in one direction by a telomere, there is often associated movements of unrelated chromosomes. In yeast we discovered that a specific region of the nucleoporin Nup2 promotes inter-chromosomal coordination. We hypothesise that Nup2 creates an interconnected meshwork between unrelated chromosomes. By exploring the mechanical aspects of chromosome motion we are gaining insight into the 4D organisation of the meiotic nucleus.