Suzuki Ayumu, Uranishi Kousuke, Nishimoto Masazumi, Mizuno Yosuke, Mizuno Seiya, Takahashi Satoru, Eisenman Robert N, Okuda Akihiko
Division of Biomedical Sciences, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama, 350-1241, Japan.
Division of Morphological Science, Biomedical Research Center, Saitama Medical University, 38 Morohongo, Moroyama, Iruma-gun, Saitama, 350-0495, Japan.
Sci Rep. 2024 Mar 4;14(1):5236. doi: 10.1038/s41598-024-55506-7.
Meiosis is a specialized type of cell division that occurs physiologically only in germ cells. We previously demonstrated that MYC-associated factor X (MAX) blocks the ectopic onset of meiosis in embryonic and germline stem cells in culture systems. Here, we investigated the Max gene's role in mouse primordial germ cells. Although Max is generally ubiquitously expressed, we revealed that sexually undifferentiated male and female germ cells had abundant MAX protein because of their higher Max gene expression than somatic cells. Moreover, our data revealed that this high MAX protein level in female germ cells declined significantly around physiological meiotic onset. Max disruption in sexually undifferentiated germ cells led to ectopic and precocious expression of meiosis-related genes, including Meiosin, the gatekeeper of meiotic onset, in both male and female germ cells. However, Max-null male and female germ cells did not complete the entire meiotic process, but stalled during its early stages and were eventually eliminated by apoptosis. Additionally, our meta-analyses identified a regulatory region that supports the high Max expression in sexually undifferentiated male and female germ cells. These results indicate the strong connection between the Max gene and physiological onset of meiosis in vivo through dynamic alteration of its expression.
减数分裂是一种特殊类型的细胞分裂，仅在生殖细胞中生理性地发生。我们之前证明，MYC相关因子X（MAX）在培养系统中阻止胚胎干细胞和生殖系干细胞中减数分裂的异位起始。在此，我们研究了Max基因在小鼠原始生殖细胞中的作用。尽管Max通常在全身广泛表达，但我们发现，由于性未分化的雄性和雌性生殖细胞中Max基因表达高于体细胞，它们具有丰富的MAX蛋白。此外，我们的数据显示，雌性生殖细胞中这种高水平的MAX蛋白在生理性减数分裂起始前后显著下降。性未分化生殖细胞中的Max缺失导致减数分裂相关基因（包括减数分裂起始的守门基因Meiosin）在雄性和雌性生殖细胞中异位和过早表达。然而，Max基因敲除的雄性和雌性生殖细胞并未完成整个减数分裂过程，而是在早期阶段停滞，并最终通过凋亡被清除。此外，我们的荟萃分析确定了一个调控区域，该区域支持性未分化的雄性和雌性生殖细胞中Max的高表达。这些结果表明，Max基因通过其表达的动态变化与体内减数分裂的生理性起始之间存在紧密联系。
