Summary Sexual reproduction requires the unique cell division called meiosis, in which a diploid cell undergoes a reductional division to generate haploid gametes. A hallmark of meiotic prophase is the formation of pairwise linkages between homologous chromosomes, which later enable them to segregate from each other. In most organisms the pairing of homologous chromosomes is reinforced by synapsis, the polymerization of the synaptonemal complex (SC) between paired chromosome axes. The primary questions addressed here are: 1) how pairing is accomplished and 2) how synapsis is regulated so that it occurs selectively between homologs. We provide evidence that a connection between the chromosomes and the microtubule cytoskeleton via a bridge across the nuclear envelope is critical for both of these mechanisms. Our results indicate the existence of a mechanism that uses dynein to assess homology before licensing SC polymerization. The molecular components of this mechanism are conserved from fungi to mammals.

Crossover recombination and the formation of chiasmata normally ensure the proper segregation of homologous chromosomes during the first meiotic division. zhp-3, the Caenorhabditis elegans ortholog of the budding yeast ZIP3 gene, is required for crossover recombination. We show that ZHP-3 protein localization is highly dynamic. At a key transition point in meiotic prophase, the protein shifts from along the length of the synaptonemal complex (SC) to an asymmetric localization on the SC and eventually becomes restricted to foci that mark crossover recombination events. A zhp-3::gfp transgene partially complements a null mutation and reveals a separation of function; although the fusion protein can promote nearly wild-type levels of recombination, aneuploidy among the progeny is high, indicating defects in meiotic chromosome segregation. The structure of bivalents is perturbed in this mutant, suggesting that the chromosome segregation defect results from an inability to properly remodel chromosomes in response to crossovers. smo-1 mutants exhibit phenotypes similar to zhp-3::gfp mutants at higher temperatures, and smo-1; zhp-3::gfp double mutants exhibit more severe meiotic defects than either single mutant, consistent with a role for SUMO in the process of SC disassembly and bivalent differentiation. We propose that coordination of crossover recombination with SC disassembly and bivalent formation reflects a conserved role of Zip3/ZHP-3 in coupling recombination with SC morphogenesis.

High-resolution time-lapse imaging of meiosis in C. elegans reveals stage-specific, dynein-driven chromosome motion that accelerates homologue pairing and triggers synapsis.