Opposing effects of retinoic acid and FGF9 on Nanos2 expression and meiotic entry of mouse germ cells
Opposing effects of retinoic acid and FGF9 on Nanos2 expression and meiotic entry of mouse germ cells
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DOI：
10.1242/jcs.057968
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发表时间：
2010-03-15
影响因子：
4
通讯作者：
Dolci, Susanna
中科院分区：
文献类型：
--
作者：
Barrios, Florencia;Filipponi, Doria;Dolci, Susanna
在小鼠中，已经鉴定出三个与果蝇纳米（Nos）基因同源的基因。其中一个基因Nanos2的缺失会导致男性不育，因为在胎儿时期会失去生殖细胞。在细胞凋亡前，无Nanos2的细胞进入减数分裂，表明Nanos2作为减数分裂抑制因子发挥作用。在这里，我们发现Nanos2在从胎儿性腺细胞到出生后的精原干细胞的男性生殖细胞中持续表达。我们观察到，促减数分裂因子AtRA，维甲酸（RA）的类似物，在胎儿和出生后的性腺细胞中下调NANOS2水平，同时促进减数分裂。有趣的是，FGF9是一种对性别分化和胎儿性腺细胞存活至关重要的生长因子，在男性和女性原始生殖细胞（PGCs）和减数分裂前精原细胞中上调NANOS2的水平。这种效应与减数分裂进入的损伤相一致，表明FGF9通过上调Nanos2作为减数分裂的抑制剂。我们发现NANOS2与PUM2相互作用，并且这两种蛋白在蔗糖梯度上共定位于核糖核颗粒和多体部分，支持它们结合RNA的观点。最后，我们发现重组NANOS2与两个参与生殖细胞分化的精原mrna Gata2和taf71结合。
In the mouse, three genes that are homologous to the Drosophila Nanos (Nos) gene have been identified. Deletion of one of these genes, Nanos2, results in male sterility, owing to loss of germ cells during fetal life. Before apoptosis, Nanos2-null gonocytes enter meiosis, suggesting that Nanos2 functions as a meiotic repressor. Here, we show that Nanos2 is continuously expressed in male germ cells from fetal gonocytes to postnatal spermatogonial stem cells. We observed that the promeiotic factor AtRA, an analog of retinoic acid (RA), downregulates NANOS2 levels, in both fetal and postnatal gonocytes, while promoting meiosis. Interestingly, FGF9, a growth factor crucial for sex differentiation and survival of fetal gonocytes, upregulates levels of NANOS2 in both male and female primordial germ cells (PGCs) and in premeiotic spermatogonia. This effect was paralleled by an impairment of meiotic entry, suggesting that FGF9 acts as an inhibitor of meiosis through the upregulation of Nanos2. We found that NANOS2 interacts with PUM2, and that these two proteins colocalize in the ribonucleoparticle and polysomal fractions on sucrose gradients, supporting the notion that they bind RNA. Finally, we found that recombinant NANOS2 binds to two spermatogonial mRNAs, Gata2 and Taf7l, which are involved in germ-cell differentiation.