Finding the correct pairing partner during meiosis: events inside and outside the nucleus

Leticia Labrador-Gonzalez¹, Consuelo Barroso¹, Nicola Silva¹, Nuria Ferrandiz-Diaz¹, James Lightfoot¹, Thomas Mueller², Donald Moerman³, Anne Villeneuve⁴ and Enrique Martinez-Perez¹ 

¹ MRC Clinical Sciences Centre, Imperial College London, UK. ² Technische Universitat, Dresden, Germany.³ University of British Columbia, Canada. ⁴ Stanford University, USA  

During meiosis, each chromosome must recognize and align with its correct pairing partner in a process known as homolog pairing. Once homology search is satisfied, homolog interactions are stabilised by the loading a proteinaceous structure called synaptonemal complex (SC). However, the SC plays no role in homology recognition and therefore pairing and SC assembly need to be coordinated to prevent the assembly of the SC between non-homologous chromosomes. In C. elegans, pairing and SC assembly occur during a stage known as transition zone, in which chromosomes are clustered inside the nucleus and one chromosomal end is attached to SUN-1 aggregates in the inner nuclear envelope. SUN-1 interacts with ZYG-12, and this conserved SUN/KASH pair is required to transmit cytoskeletal forces to the chromosomes, resulting in rapid chromosome movements. However, the exact roles that chromosome movements play for pairing and SC assembly are not well understood. During a screen for crossover deficient mutants, we isolated a new allele of spd-3, spd-3(me85), a gene that had previously been involved in spindle alignment in the early embryonic divisions. While the mitotic defects present in spd-3 null mutants prevent the study of meiosis in these worms, our analysis of spd-3(me85) demonstrates that SPD-3 plays crucial roles during meiotic prophase. Although the SC is normally formed in spd-3(me85) mutants, FISH analysis of three different chromosomes reveals a strong pairing defect, demonstrating the presence of extensive non-homologous synapsis. Despite this pairing defect, chromosomes are successfully attached to SUN-1 aggregates in spd-3(me85) mutants and cytoskeletal motors are recruited to the outside of the nuclear envelope, but  live-imaging of SUN-1 aggregates demonstrates an impairment of chromosome movements in transition zone nuclei. Surprisingly, SPD-3 localizes to mitochondria, suggesting that SPD-3 acts upstream of cytoskeletal motors to promote chromosome movements and that these movements are required for pairing but not for SC assembly.  Furthermore, we will also show that the HORMA-domain protein HTP-1 (a conserved component of axial elements) actively controls exit from transition zone, preventing SC assembly and elongating the time during which SUN-1-driven chromosome movements can promote homolog pairing.

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Last updated: Friday, 28 September 2012