Dazl determines primordial follicle formation through the translational regulation of Tex14.
Dazl determines primordial follicle formation through the translational regulation of Tex14.
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Dazl 通过 Tex14 的翻译调节来确定原始卵泡的形成。
DOI：
10.1096/fj.201901247r
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Rosario R
中科院分区：
文献类型：
--
作者：
Rosario R
无精子样缺失(DAZL)是一种生殖细胞RNA结合蛋白，在进入和进行减数分裂过程中是必不可少的。由于减数分裂不完全，DAZL基因敲除小鼠的表型有广泛的生殖细胞损失。我们已经在小鼠胚胎卵巢培养中使用短干扰RNA敲除建立了DAZL低畸形模型，从而可以研究DAZL在生殖细胞成熟中的功能。DAZL低形态卵巢表现为受损性生殖细胞巢破裂，卵泡总数减少66%，原始卵泡比例增加，卵泡内有较小的卵母细胞。没有明显的早期生殖细胞丢失或减数分裂延迟。细胞间桥成分睾丸表达蛋白(Tex)14的免疫染色显示，∼的病灶数量和大小减少了59%，而Tex14mRNA的水平没有任何变化。TEX14在人胚胎卵巢中的表达也得到证实。利用3‘UTR-荧光素酶报告基因分析，证实TEX14的翻译调控是DAZL依赖的。因此，DAZL对于生殖细胞巢内正常的细胞间桥和它们的及时分解是必不可少的，并对PMF的后续组装产生重大影响。-Rosario，R.，Crichton，J.H.，Stewart，H.L.，Childs，A.J.，Adams，I.R.，Anderson，R.A.DAZL通过Tex14的翻译调控决定原始毛囊的形成。
Deleted in azoospermia-like (DAZL) is a germ cell RNA-binding protein that is essential for entry and progression through meiosis. The phenotype of the Dazl knockout mouse has extensive germ cell loss because of incomplete meiosis. We have created a Dazl hypomorph model using short interfering RNA knockdown in mouse fetal ovary cultures, allowing investigation of Dazl function in germ cell maturation. Dazl hypomorph ovaries had a phenotype of impaired germ cell nest breakdown with a 66% reduction in total follicle number and an increase in the proportion of primordial follicles (PMFs), with smaller oocytes within these follicles. There was no significant early germ cell loss or meiotic delay. Immunostaining of intercellular bridge component testis-expressed protein (Tex)14 showed ∼59% reduction in foci number and size, without any change in Tex14 mRNA levels. TEX14 expression was also confirmed in the human fetal ovary across gestation. Using 3′UTR-luciferase reporter assays, translational regulation of TEX14 was demonstrated to be DAZL-dependant. Dazl is therefore essential for normal intercellular bridges within germ cell nests and their timely breakdown, with a major impact on subsequent assembly of PMFs.—Rosario, R., Crichton, J. H., Stewart, H. L., Childs, A. J., Adams, I. R., Anderson, R. A. Dazl determines primordial follicle formation through the translational regulation of Tex14.