A germ cell determinant reveals parallel pathways for germ line development in Caenorhabditis elegans
A germ cell determinant reveals parallel pathways for germ line development in Caenorhabditis elegans
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DOI：
10.1242/dev.125732
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发表时间：
2015-10-15
期刊：
影响因子：
4.6
通讯作者：
Yanowitz, Judith L.
中科院分区：
文献类型：
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作者：
Mainpal, Rana;Nance, Jeremy;Yanowitz, Judith L.
尽管生殖细胞对于遗传物质的传递至关重要，但我们对控制原始生殖细胞（PGC）特化和分化的分子程序的理解是有限的。在这里，我们提出的研究结果，X染色体不分离因子-1（XND-1），已知其在调节减数分裂交叉形成的作用，是秀丽隐杆线虫生殖细胞命运的早期决定因素。xnd-1突变胚胎显示出一种新的“单一PGC”表型，这是P-4卵裂球G2期细胞周期停滞的结果。幼虫和成虫显示较小的生殖系和减少的育雏大小与XND-1在生殖细胞增殖中的作用一致。母体XND-1蛋白存在于P-4谱系中，并且仅定位于PGCs、Z2和Z3中的细胞核。合子XND-1在此后不久，在类似于300-细胞阶段开启，使得XND-1成为蠕虫PGCs中最早的合子表达基因。引人注目的是，xnd-1突变体的一个子集缺乏生殖细胞，这是一种与nos-2共有的表型，nos-2是保守的Nanos家族的成员。我们产生了一个nos-2无效等位基因，并显示nos-2; xnd-1双突变体显示合成不育。进一步去除nos-1会导致几乎完全不育，绝大多数动物都没有生殖细胞。xnd-1突变体的不育性与转录激活相关的组蛋白修饰增加和体细胞转基因的异常表达相关。总之，这些数据有力地表明，xnd-1定义了PGC发展的一个新的分支，其与nos-2和nos-1冗余地发挥作用，通过维持转录静止和调节生殖细胞增殖来促进生殖细胞命运。
Despite the central importance of germ cells for transmission of genetic material, our understanding of the molecular programs that control primordial germ cell (PGC) specification and differentiation are limited. Here, we present findings that X chromosome NonDisjunction factor-1 (XND-1), known for its role in regulating meiotic crossover formation, is an early determinant of germ cell fates in Caenorhabditis elegans. xnd-1 mutant embryos display a novel 'one PGC' phenotype as a result of G2 cell cycle arrest of the P-4 blastomere. Larvae and adults display smaller germ lines and reduced brood size consistent with a role for XND-1 in germ cell proliferation. Maternal XND-1 proteins are found in the P-4 lineage and are exclusively localized to the nucleus in PGCs, Z2 and Z3. Zygotic XND-1 turns on shortly thereafter, at the similar to 300-cell stage, making XND-1 the earliest zygotically expressed gene in worm PGCs. Strikingly, a subset of xnd-1 mutants lack germ cells, a phenotype shared with nos-2, a member of the conserved Nanos family of germline determinants. We generated a nos-2 null allele and show that nos-2; xnd-1 double mutants display synthetic sterility. Further removal of nos-1 leads to almost complete sterility, with the vast majority of animals without germ cells. Sterility in xnd-1 mutants is correlated with an increase in transcriptional activation-associated histone modification and aberrant expression of somatic transgenes. Together, these data strongly suggest that xnd-1 defines a new branch for PGC development that functions redundantly with nos-2 and nos-1 to promote germline fates by maintaining transcriptional quiescence and regulating germ cell proliferation.