Investigating meiotic chromosome structure during meiotic prophase in C. elegans
File(s)
Author(s)
Jaso Tamame, Angel Luis
Type
Thesis or dissertation
Abstract
Meiosis is the specialised cell division program that allows the formation of haploid
gametes from diploid germ cells, playing an essential role in the life cycle of sexuallyreproducing
organisms. Meiosis involves dramatic changes in chromosome structure
during the long prophase that precedes the first meiotic division. At the onset of meiosis
axial elements (AE) containing cohesin, the complex that provides sister chromatid
cohesion (SCC), are established along each chromosome. Following AE assembly,
homologous chromosomes pair with one another and crossover (CO) recombination
events are formed between them. COs, together with SCC, provide the basis of
chiasmata: temporary physical attachments between homologous chromosomes that
ensure their correct orientation on the first meiotic spindle. Therefore, COs play an
essential role during meiosis and their number and position appear to be highly
regulated. However, the functional interplay between chromosome structure and CO
formation and distribution remains poorly understood. In this project, I have combined
the experimental advantages of the C. elegans germ line with super resolution
microscopy (SRM) techniques to study the structural changes that chromosomes
undergo during meiotic prophase. I develop methods to image three-dimensionally
intact meiotic nuclei using structural illumination microscopy (SIM) and Imaris image
software analysis, making it possible to measure structural features of individual meiotic
chromosomes, including CO sites. When combined with the extensive genetic resources
available in C. elegans, this method provides a powerful tool to investigate the functional
regulation of meiotic chromosome structure by different protein complexes such as
cohesin. I also describe that a mutation in MEI-2, a component of the microtubule
severing complex katanin, results in altered CO distribution, likely by affecting early
steps of meiotic recombination. This finding reveals an unexpected role for katanin
during meiotic prophase and suggests that the microtubule network plays an important
role in the regulation of CO distribution.
gametes from diploid germ cells, playing an essential role in the life cycle of sexuallyreproducing
organisms. Meiosis involves dramatic changes in chromosome structure
during the long prophase that precedes the first meiotic division. At the onset of meiosis
axial elements (AE) containing cohesin, the complex that provides sister chromatid
cohesion (SCC), are established along each chromosome. Following AE assembly,
homologous chromosomes pair with one another and crossover (CO) recombination
events are formed between them. COs, together with SCC, provide the basis of
chiasmata: temporary physical attachments between homologous chromosomes that
ensure their correct orientation on the first meiotic spindle. Therefore, COs play an
essential role during meiosis and their number and position appear to be highly
regulated. However, the functional interplay between chromosome structure and CO
formation and distribution remains poorly understood. In this project, I have combined
the experimental advantages of the C. elegans germ line with super resolution
microscopy (SRM) techniques to study the structural changes that chromosomes
undergo during meiotic prophase. I develop methods to image three-dimensionally
intact meiotic nuclei using structural illumination microscopy (SIM) and Imaris image
software analysis, making it possible to measure structural features of individual meiotic
chromosomes, including CO sites. When combined with the extensive genetic resources
available in C. elegans, this method provides a powerful tool to investigate the functional
regulation of meiotic chromosome structure by different protein complexes such as
cohesin. I also describe that a mutation in MEI-2, a component of the microtubule
severing complex katanin, results in altered CO distribution, likely by affecting early
steps of meiotic recombination. This finding reveals an unexpected role for katanin
during meiotic prophase and suggests that the microtubule network plays an important
role in the regulation of CO distribution.
Version
Open Access
Date Issued
2018-12
Date Awarded
2019-08
Copyright Statement
Creative Commons Attribution NonCommercial Licence
Advisor
Martinez-Perez, Enrique
Publisher Department
Institute of Clinical Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)