Academic journal article Genetics

Manipulation of Karyotype in Caenorhabditis Elegans Reveals Multiple Inputs Driving Pairwise Chromosome Synapsis during Meiosis

Academic journal article Genetics

Manipulation of Karyotype in Caenorhabditis Elegans Reveals Multiple Inputs Driving Pairwise Chromosome Synapsis during Meiosis

Article excerpt

SEGREGATION of homologous chromosomes is a central defining event of meiosis, the specialized cell division program that allows sexually reproducing organisms to reduce their diploid chromosome complement to produce haploid gametes. In order to segregate away from each other, homologous chromosomes must recognize and align with their correct pairing partners during meiotic prophase to allow meiotic recombination to create physical attachments (chiasmata). These physical links between homologs will then promote their correct orientation on the metaphase plate of the meiosis I spindle and ensure their proper partitioning during the first meiotic division. At center stage during the events that prepare homologous chromosomes for segregation is a highly ordered proteinaceous structure called the synaptonemal complex (SC). The SC is composed of two lateral elements that form along the axis of each homolog, linked together by the SC central region. The SC has been shown to be a major regulator of the complex behavior of meiotic chromosomes, acting to stabilize and maintain tight associations between the homologs and playing a role in the maturation of recombination intermediates into fully functional chiasmata.

The nematode Caenorhabditis elegans has emerged as one the premier model systems for investigating key meiotic events, including the mechanisms regulating assembly of the SC (a process known as synapsis). The C. elegans adult hermaphrodite has two gonads, each containing hundreds of germ-cell nuclei that enter and progress through the meiotic prophase program as they travel from the distal tip of the gonad to the uterus. A full gonad therefore represents a developmental time course of nuclei at various stages of meiotic prophase that are organized in a spatiotemporal gradient highly amenable to imaging of meiotic chromosome structures in both live and fixed samples. Moreover, cytological analysis of meiosis can be coupled with genetic screens (Villeneuve 1994; Kelly et al. 2000; Nabeshima et al. 2004) and mutant analyses to discover and characterize the roles of components of the meiotic machinery. This powerful combination of genetics and cytology has enabled discovery of a complex network of factors regulating homolog pairing and synapsis. These include specialized chromosomal sites called "pairing centers" (PCs), located near one end of each chromosome (Rosenbluth and Baillie 1981; Rose et al. 1984; McKim et al. 1988, 1993; Villeneuve 1994), that mediate chromosome movements that are important both for achieving timely homolog pairing and for constraining SC assembly to occur exclusively between correctly paired homologs (MacQueen et al. 2005; MartinezPerez and Villeneuve 2005; Phillips et al. 2005; Penkner et al. 2007, 2009; Sato et al. 2009).

C. elegans is also amenable to a complementary approach that enables investigation of meiotic mechanisms in the context of a full wild-type complement of meiotic machinery components. This approach involves the use of modified karyotypes, including altered ploidy, as triploid (3n) and tetraploid (4n) worms are viable. Analysis of pairing and synapsis in such challenged situations has provided insights into the principles governing these processes (Mlynarczyk-Evans et al. 2013). For example, this approach revealed that when more than two partners can compete for synapsis, chromosomes are initially sorted into homologous groups regardless of chromosome number and then eventually commit into exclusively pairwise synapsis associations. This study also provided evidence for the operation of "masking mechanisms" that are capable of counterbalancing stringent quality control systems to promote reproductive success. Further, this prior work suggested that experiments integrating the use of altered ploidy with genetic mutants and/or transgenes expressing cytological markers might have potential to generate important new insights into the mechanisms and regulation of meiosis. However, the feasibility of integrating these approaches was limited by the substantial technical difficulty of generating polyploid worms of the desired genotypes. …

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