Stereotypical execution of gametogenesis requires orchestration of many developmental and molecular pathways. Among these, the Ras/Extracellular signal-regulated kinase (ERK) signaling pathway governs a wide array of cellular processes, including many that occur during oogenesis. Meiosis is a key cellular and molecular process that produces haploid gametes and ensures genetic diversity in sexually reproducing organisms. Inappropriate execution of any step during meiosis I leads to failures in chromosome segregation, often resulting in aneuploidy or severe developmental disorders such as the Down's syndrome. Many studies have shown that structural constraints between the chromosomes play central roles in meiotic progression. However, the function of signaling pathways in regulating synapsis and recombination remains unknown. Using C. elegans as our model system, we determined that the timely activation and inactivation of ERK, the most downstream kinase in the core Ras/ERK pathway, are important for proper synaptonemal complex (SC) dynamics. Absence of ERK activity results in extensive asynapsis in the pachytene region, while constant activation of ERK at the loop region leads to defects in SC disassembly. Additionally, through a functional genomic screen for targets of ERK that govern oogenesis, we identified RbAp46 homolog, RBA-1 as a direct in vitro substrate of ERK. Loss of
rba-1 causes increased asynapsis in pachytene zone, resulting in increased apoptosis, increased embryonic lethality and eventually sterility. Genetic analysis of the
rba-1 and ras gain-of-function double mutant showed that RBA-1 functions downstream of ERK in regulating the maintenance of SC. RbAp46 is thought to function as part of the Polycomb Repressive Complex 2 (PRC2) in flies and mammals. PRC2 regulates the deposition of Histone H3 K9 and K27 tri-methylation, both of which are repressive marks involved in facultative gene silencing. Interestingly however, we find that loss of
rba-1 does not impact either H3K9me3 or H3K27me3 in C. elegans germline, neither does it affect gene expression as assayed via RNA Seq analysis. However, loss of
lin-53, a homolog of RbAp48 and a paralog of
rba-1, leads to complete loss of both H3K9me3 and H3K27me3, but does not impact synapsis. These results suggest that RBA-1 regulates synapsis independent of PRC2 function and gene expression, but likely through chromosome compaction or nucleosome positioning. Together, our data provide the first direct link between the Ras/ERK pathway and regulation of synaptonemal complex dynamics via RbAp46.