Zebrafish lack a strong meiotic checkpoint response to defects in chromosome synapsis

Abstract

The synaptonemal complex (SC) is a meiosis-specific structure that aligns homologous chromosomes and facilitates the repair of meiotic DNA double-strand breaks (DSBs). Defects in SC assembly or unrepaired DSBs trigger a prophase I checkpoint to prevent the formation of aneuploid gametes. The strength of these checkpoints varies among species and between sexes. Whether zebrafish (Danio rerio) have prophase I surveillance mechanisms that monitor chromosome synapsis and/or meiotic DSB repair has not been explored. To investigate how defects in SC formation affect gametogenesis in zebrafish, mutations in genes encoding two structural components of the SC, syce2 and sycp1 were examined. While syce2 and sycp1 fish exhibit defects in both synapsis and DSB repair, the two mutants show different reproductive outcomes. syce2 mutant females and males produce a significant percentage of normal progeny. In contrast, sycp1 mutant females produce fewer normal offspring, while sycp1 mutant males are infertile, with spermatocytes arrested at metaphase I. Notably, offspring from syce2 and sycp1 mutant mothers show extensive somatic mosaic aneuploidy, indicating that defects in the meiotic machinery can lead to genome instability during embryogenesis. Our findings suggest that a checkpoint monitoring the progression of synapsis may be weak or absent in the zebrafish, resembling the situation in yeast, plants, and Drosophila, rather than in mice and the nematode Caenorhabditis. elegans where robust mechanisms exists to silence unpaired chromosomes leading to meiocyte apoptosis. Author SummaryMeiosis is a specialized cell division that reduces chromosome numbers for the production of haploid gametes and is necessary for sexual reproduction. During meiosis prophase I, precise coordination is required for key events such as the formation and repair of DNA double-strand breaks and the synapsis of homologous chromosomes, which is mediated by the synaptonemal complex. Specialized checkpoint pathways monitor the proper execution of these events. Errors in either process can induce a checkpoint response leading to cell death or the production of aneuploid gametes. Here, we demonstrate that the checkpoint monitoring synapsis is weak--or potentially absent--in zebrafish, suggesting that a robust synapsis checkpoint is not conserved across all vertebrates. We discuss this finding in the context of the teleost-specific whole genome duplication and the widespread heterogametic switching (e.g., XY to ZW systems) within this diverse clade, which includes over 30,000 species.