Faithful segregation of chromosomes at the first meiotic division is dependent on proper homologous pairing and synapsis. In C. elegans, specific regions on each chromosome, called Pairing Centers, recruit a family of zinc-finger proteins including ZIM-1, 2, 3 and HIM-8. Pairing Centers are essential for linking chromosomes to the microtubule cytoskeleton, thereby facilitating chromosome motion required for the proper coordination of pairing and synapsis.
Specific nuclear envelope proteins, as well as dynein, aggregate at sites of Pairing Centers in early prophase. Recent work from our lab has shown that inner nuclear membrane protein SUN-1 and the KASH-domain bearing protein ZYG-12 are required for homolog recognition; in their absence, chromosomes fail to pair and undergo inappropriate synapsis with nonhomologous partners. In contrast, loss of dynein results in extensive asynapsis, though chromosomes do pair with their homologs, suggesting that dynein function is essential for synapsis initiation. Taken together, these results support a model in which SUN-1 and ZYG-12 impose a barrier to synapsis that must be overcome by dynein to coordinate pairing and synapsis in early prophase. How nuclear envelope proteins, like SUN-1 and ZYG-12, inhibit synapsis and promote homolog pairing remain to be determined.
A candidate screen for new factors involved in meiotic chromosome dynamics revealed a potential role for SPD-3 in pairing and synapsis. A temperature-sensitive allele, oj35
, results in variable meiotic defects when shifted to the restrictive temperature (25 deg C) at the L4 stage. To deplete SPD-3 more completely, I performed RNAi in spd-3
) mutants at the restrictive temperature. spd-3
, RNAi) mutants undergo extensive nonhomologous synapsis in pachytene, similar to that seen in sun-1
loss of function mutants, indicating that SPD-3 may play a similar role in coordinating pairing and synapsis. Unlike sun-1
(lof) mutants, however, synapsis does not occur immediately upon meiotic entry. Instead, chromosomes remain asynapsed for some time even if they have paired with their homologs. Previous studies showed that SPD-3 is required for proper spindle alignment in the early embryo and polar body extrusion in meiosis (Dinkelmann et al, 2007). SPD-3::GFP localizes to mitochondria in both embryos and the germline. How a mitochondrial protein affects chromosome dynamics within the nucleus may shed light on the mechanism by which pairing and synapsis are coordinated. I am continuing to analyze spd-3
mutants and generating an antibody against the SPD-3 protein to look at its endogenous localization, and will present my latest findings.