Olaya Iván, Yilmaz Ilara N, Nour-Kasally Naima, Charboneau Ross E, Draper Bruce W, Burgess Sean M
Department of Molecular and Cellular Biology, University of California Davis, Davis, California, United States of America.
Integrative Genetics and Genomics Graduate Group, University of California Davis, Davis, California, United States of America.
PLoS Genet. 2025 Sep 5;21(9):e1011656. doi: 10.1371/journal.pgen.1011656. eCollection 2025 Sep.
The synaptonemal complex (SC) is a meiosis-specific structure that aligns homologous chromosomes and promotes the repair of meiotic DNA double-strand breaks (DSBs). To investigate how defects in SC formation affect gametogenesis in zebrafish, we analyzed mutations in two genes encoding core SC components: syce2 and sycp1. In syce2 mutants, chromosomes exhibit partial synapsis, primarily at sub-telomeric regions, whereas sycp1 mutant chromosomes display early prophase co-alignment but fail to synapse. Both mutants exhibit reduced efficiency in repairing meiotic DSBs compared to wild type. Despite these defects, syce2 and sycp1 mutant females are fertile. However, sycp1 mutant females produce a higher proportion of malformed progeny, correlating with increased univalent formation. While syce2 mutant males are fertile and produce normal offspring, sycp1 mutant males are sterile, with spermatocytes that transit prophase I but arrest at metaphase I or II. Additionally, sycp1 mutants display a male-biased sex ratio that can be suppressed by extending the developmental window for sex determination, suggesting that the absence of synapsis delays-but does not completely block-meiotic progression. Notably, embryos from syce2 and sycp1 mutant females exhibit widespread somatic mosaic aneuploidy, indicating that impaired meiotic chromosome dynamics can compromise genome stability during early development. In contrast to mouse SC mutants, the zebrafish syce2 and sycp1 mutants examined in this study progress through meiotic prophase I with minimal disruption, suggesting a less stringent surveillance mechanism for synapsis errors in zebrafish.
联会复合体（SC）是一种减数分裂特异性结构，它使同源染色体对齐并促进减数分裂DNA双链断裂（DSB）的修复。为了研究SC形成缺陷如何影响斑马鱼的配子发生，我们分析了编码核心SC成分的两个基因syce2和sycp1中的突变。在syce2突变体中，染色体表现出部分联会，主要发生在亚端粒区域，而sycp1突变体染色体在前期早期共对齐，但未能联会。与野生型相比，这两种突变体在修复减数分裂DSB方面的效率均降低。尽管存在这些缺陷，syce2和sycp1突变体雌性仍可育。然而，sycp1突变体雌性产生的畸形后代比例更高，这与单价体形成增加相关。虽然syce2突变体雄性可育并产生正常后代，但sycp1突变体雄性不育，其精母细胞进入前期I，但在中期I或II停滞。此外，sycp1突变体表现出雄性偏向的性别比例，通过延长性别决定的发育窗口可以抑制这种现象，这表明联会缺失会延迟但不会完全阻断减数分裂进程。值得注意的是，来自syce2和sycp1突变体雌性的胚胎表现出广泛的体细胞镶嵌非整倍性，这表明减数分裂染色体动力学受损会在早期发育过程中损害基因组稳定性。与小鼠SC突变体不同，本研究中检测的斑马鱼syce2和sycp1突变体在减数分裂前期I中进展时受到的干扰最小，这表明斑马鱼对联会错误的监测机制不那么严格。
