After they have replicated, homologous chromosomes pair, synapse and recombine in meiotic prophase. These events ensure that chromosomes segregate properly to produce eggs and sperm with the correct number of chromosomes. We are interested in understanding how defects in these processes are monitored to make sure that they occur correctly and avoid the production of aneuploid gametes.

If chromosomes don’t synapse, they missegregate during meiosis and produce aneuploid eggs and sperm. We have shown that meiotic nuclei with unsynapsed chromosomes activate apoptosis (see Figure 1), indicating that a checkpoint monitors whether chromosomes have synapsed. We are further characterizing this meiotic checkpoint. Specifically, we want to know: 1) what signal is generated by unsynapsed chromosomes to activate this meiotic checkpoint; 2) how this signal is silenced during a normal meiosis; and 3) how this signal is transduced to promote apoptosis of defective nuclei. In mitosis, checkpoints have been shown to play an important role in genomic stability and preventing cancer. We predict that analysis of this meiotic checkpoint will reveal common mechanisms that contribute to maintaining genomic integrity and preventing aneuploidy.

Asynapsis of a single pair of chromosomes results in apoptosis in C. elegans. Unsynapsed chromosomes are visualized as segments of HTP-3 (red) staining devoid of SYP-1 (green). A single pair of unsynapsed chromosomes (arrow) is visible in a nucleus completely encircled by a GFP reporter (white) that identifies apoptotic nuclei. Surrounding nuclei have achieved complete homolog synapsis and do not exhibit GFP staining.

The C. elegans germline provides a unique opportunity to investigate the temporal coordination of meiotic prophase events. For example, proteins required for proper regulation of meiotic recombination, such as PCH-2 and ZHP-3, localize to meiotic nuclei during specific stages of meiotic prophase and are either removed or relocalize in response to successful meiotic recombination. When meiotic recombination is defective, these proteins fail to be removed or relocalize, suggesting that their persistence on meiotic chromosomes indicate the activation of feedback mechanisms that maintain competence for meiotic recombination (See Figure 2). We are interested in the mechanisms that regulate these changes in localization and how they might contribute to the regulation of meiotic recombination.

PCH-2 remains on meiotic chromosomes when there are defects in recombination.
Germlines from wildtype (top) and meDf2 mutant (bottom) were stained with DAPI (red) and an antibody against PCH-2 (green). PCH-2 is absent from nuclei in late pachytene (brackets) in wildtype germlines but persists into late pachytene in meDf2 mutant germlines.