Loss of Gsdf leads to a dysregulation of Igf2bp3-mediated oocyte development in medaka
Loss of Gsdf leads to a dysregulation of Igf2bp3-mediated oocyte development in medaka
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Gsdf 缺失导致 Igf2bp3 介导的青鳉卵母细胞发育失调
DOI：
10.1016/j.ygcen.2019.04.001
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发表时间：
2019-06-01
影响因子：
2.7
通讯作者：
Guan, Guijun
中科院分区：
文献类型：
--
作者：
Wu, Xiaowen;Zhang, Yingqing;Guan, Guijun
性腺体细胞衍生因子（Gsdf）是青鳉（Oryzias latipes）卵巢和睾丸发育所必需的一种TGF-β 3因子。然而，受Gsdf信号转导调控的下游基因仍然未知。使用高通量蛋白质组学方法，我们确定了一个显着增加的gsdf缺陷卵巢中的RNA结合蛋白Igf 2bp 3的表达。我们使用实时PCR定量和蛋白质印迹法验证了这种转录和蛋白质表达对正常性腺的差异。igf 2bp 3的基因组结构和同线侧翼片段在鱼类和哺乳动物中高度保守。igf 2bp 3表达与卵母细胞发育相关，这与igf 2bp 3直系同源物Vg 1-RBP/Vera在非洲爪蟾中的表达一致。与正常卵巢相比，在一个月大的gsdf缺陷卵巢中，H3 K27 me 3和Igf 2bp 3阳性生殖细胞的包囊显著增加，表明gsdf耗尽导致Igf 2bp 3介导的卵母细胞发育失调。我们的研究结果提供了新的见解Gsdf-Igf 2bp 3信号转导机制的基础配子发生的基本过程，这些机制可能是很好地保存跨门。
Gonadal soma-derived factor (Gsdf) is a unique TGF-f3 factor essential for both ovarian and testicular development in Hd-rR medaka (Oryzias latipes). However, the downstream genes regulated by Gsdf signaling remain unknown. Using a high-throughput proteomic approach, we identified a significant increase in the expression of the RNA-binding protein Igf2bp3 in gsdf-deficient ovaries. We verified this difference in transcription and protein expression against normal gonads using real-time PCR quantification and Western blotting. The genomic structure of igf2bp3 and the syntenic flanking segments are highly conserved across fish and mammals. igf2bp3 expression was correlated with oocyte development, which is consistent with the expression of the igf2bp3 ortholog Vg1-RBP/Vera in Xenopus. In contrast to the normal ovary, cysts of H3K27me3- and Igf2bp3-positive germ cells were dramatically increased in the one-month-old gsdf-deficient ovary, indicating that the gsdf depletion led to a dysregulation of Igf2bp3-mediated oocyte development. Our results provide novel insights into the Gsdf-Igf2bp3 signaling mechanisms that underlie the fundamental process of gametogenesis; these mechanisms may be well conserved across phyla.