Meiotic chromosomes in motion: a perspective from Mus musculus and Caenorhabditis elegans

Abstract

Vigorous chromosome movement during the extended prophase of the first meiotic division is conserved in most eukaryotes. The movement is crucial for the faithful segregation of homologous chromosomes into daughter cells, and thus for fertility. A prerequisite for meiotic chromosome movement is the stable and functional attachment of telomeres or chromosome ends to the nuclear envelope and their cytoplasmic coupling to the cytoskeletal forces responsible for generating movement. Important advances in understanding the components, mechanisms, and regulation of chromosome end attachment and movement have recently been made. This review focuses on insights gained from experiments into two major metazoan model organisms: the mouse, Mus musculus, and the nematode, Caenorhabditis elegans.

Keywords: C. elegans; Chromosome movement; LINC complex; Meiosis; Mouse.

Fig. 1

Schematic representation of chromosome dynamics during prophase of the first meiotic division. In C. elegans (top panel), one chromosome end is tethered to the nuclear envelope (NE). During leptonema/zygonema, the chromatin clusters at one side of the nucleus. At this stage, rapid prophase movements (RPMs) are most prominent. SUN-1 aggregates move at an average speed of 125 nm/s; however, single highly mobile chromosome ends with a speed of up to 400 nm/s have been measured. Also, synaptonemal complex assembly is initiated at this stage. In pachytene nuclei, synaptonemal complex formation is completed to stably connect homologous chromosomes and allow the single obligate crossover event to occur. At this time, movement of the attached X-chromosome end is still observed, with an average speed of 60 nm/s. During diplotene, the synaptonemal complex is restructured as the central element components retract to the short arm of the bivalent, as defined by the crossover site. In the mouse (bottom panel), both chromosome ends are tethered to the NE in leptonema and active telomere dynamics are observed. Telomere velocities temporarily slow down during the bouquet stage at leptotene/zygotene transition and are maximal during zygonema (average speed 109 nm/s). At this time, the alignment of homologous chromosomes has been established and synaptonemal complex assembly is ongoing. Telomere movement is drastically reduced during pachynema, when the telomeres are again dispersed along the entire NE and homologous chromosomes are fully synapsed. During diplonema, the synaptonemal complex begins to disassemble, with chiasmata indicating crossover sites. Subsequently, telomeres are detached from the NE. Chromosome end velocities for both species are indicated by the dark grey area (y-axis: chromosome end velocities in nm/s, drawn not to scale)

Fig. 2

Schematic representation of the machinery involved in meiotic chromosome-end attachment and movement in the mouse (a) and in C. elegans (b). a) After cap exchange, the mature telomere-attachment complex in mouse comprises TERB1, TERB2, and MAJIN. TERB2 and MAJIN can both interact directly with telomeric DNA, thus mediating the interaction between the telomere and SUN1. The LINC complex itself, connecting to dynein and the microtubule network, consists of SUN1/2 in the inner nuclear membrane (INM) and KASH5 in the outer nuclear membrane (ONM). TRF1 is displaced from the actual site of telomere attachment during cap exchange and is replaced by MAJIN in interacting with telomeric DNA. CDK activity is implicated in regulating cap exchange and perhaps also stability of the SUN1–KASH5 interaction or meiotic membrane integrity. b) In C. elegans, the pairing centers (PCs), located in the subtelomeric region of one chromosome end, interact with the PC zinc-finger proteins. The PCs serve as recruitment sites for PLK-2, which is primed by PC protein phospho-modifications by the CHK-2 kinase. PLK-2 recruitment correlates with SUN-1 aggregation, and known substrates are SUN-1 and LMN-1. Additional, yet unidentified, adaptor proteins involved in coupling SUN-1 to chromatin or to ZIMs may exist. SUN-1 interacts with ZYG-12 in the ONM, which in turn connects to dynein, which mediates the interaction with the microtubule network

Fig. 3

Time-lapse images of Cy3-dUTP-labeled X-chromosomes in two leptotene/zygotene nuclei (a–e; a′–e′). Live imaging of Cy3-dUTP-labeled X-chromosomes (magenta) in sun-1::gfp (green) worms reveals that the attached chromosome end, which colocalizes with SUN-1 aggregates, moves vigorously within the nuclear envelope, while the remainder of the labeled chromosome remains relatively static. In some nuclei, a large proportion of non-paring center (PC) chromosome ends seems to be in contact with the nuclear periphery (a′–e′). The asterisks indicate the mobile chromosome end that is attached to the nuclear envelope by the PC. Time stamps are shown in min/s. Scale bar 2 μm