The RNA-binding protein Igf2bp3 is critical for embryonic and germline development in zebrafish
The RNA-binding protein Igf2bp3 is critical for embryonic and germline development in zebrafish
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RNA 结合蛋白 Igf2bp3 对于斑马鱼胚胎和种系发育至关重要
DOI：
10.1101/2020.06.23.167163
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Vong Y
中科院分区：
文献类型：
--
作者：
Vong Y
繁殖能力在生命的所有分支中都是必不可少的。在后生动物中，这一过程是由生殖系的形成开始的，生殖系是一组注定要形成未来性腺的细胞，性腺是产生配子的组织。种系形成的分子机制因物种而异。在斑马鱼中，生殖细胞的发育依赖于称为原始生殖细胞（PGCs）的祖细胞的特化、迁移和增殖。PGC的特化依赖于母体提供的核糖核蛋白（RNP）的细胞质复合物，即种质。在这里，我们表明，保守的RNA结合蛋白（RBP），Igf2bp3，在早期胚胎发育和种系发育过程中具有重要作用。Igf2bp3的缺失导致早期胚胎中卵黄合胞体层（YSL）扩大，生殖系RNA表达减少，以及生殖系发育失调。我们发现，母亲Igf2bp3功能的损失导致翻译失调的Nodal报告在中期囊胚过渡。此外，母系f2bp3突变体表现出种质转录本表达减少，趋化因子导向缺陷，异常PGC行为和生殖细胞死亡。因此，f2bp3突变体成年后表现出强烈的雄性偏好。我们的研究结果表明，Igf2bp3对正常的胚胎和生殖系发育是必不可少的，并作为性发育的关键调节因子。
The ability to reproduce is essential in all branches of life. In metazoans, this process is initiated by formation of the germline, a group of cells that are destined to form the future gonads, the tissue that will produce the gametes. The molecular mechanisms underlying germline formation differs between species. In zebrafish, development of the germline is dependent on the specification, migration and proliferation of progenitors called the primordial germ cells (PGCs). PGC specification is dependent on a maternally provided cytoplasmic complex of ribonucleoproteins (RNPs), the germplasm. Here, we show that the conserved RNA-binding protein (RBP), Igf2bp3, has an essential role during early embryonic development and germline development. Loss of Igf2bp3 leads to an expanded yolk syncytial layer (YSL) in early embryos, reduced germline RNA expression, and mis-regulated germline development. We show that loss of maternal Igf2bp3 function results in translational de-regulation of a Nodal reporter during the mid-blastula transition. Furthermore, maternaligf2bp3mutants exhibit reduced expression of germplasm transcripts, defects in chemokine guidance, abnormal PGC behavior and germ cell death. Consistently, adultigf2bp3mutants show a strong male bias. Our findings suggest that Igf2bp3 is essential for normal embryonic and germline development, and acts as a key regulator of sexual development.
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