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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DOI：
10.1371/journal.pgen.1009667
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发表时间：
2021-07
期刊：
影响因子：
4.5
通讯作者：
Sampath K
中科院分区：
文献类型：
--
作者：
Vong YH;Sivashanmugam L;Leech R;Zaucker A;Jones A;Sampath K
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，母体igf2bp3突变体表现出种质转录物表达减少，趋化因子指导缺陷，异常PGC行为和生殖细胞死亡。同样，成年igf2bp3突变体显示出强烈的雄性偏好。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。动物从一个卵细胞发育而来，卵细胞通过精子受精，形成各种组织和器官。不同的组织是如何形成的仍然没有完全弄清楚。特别是，我们不知道生物体是如何发展成为雄性或雌性的，也不知道种群中的性别比例是如何保持平衡的。然而，如果这些过程被破坏，种群中可能会出现过多的雄性或雌性，这可能导致无法产生下一代，最终导致物种灭绝。因此，确定允许这些过程正确发生的因素并破译它们如何运作至关重要。我们已经在热带鱼中发现了一种名为Igf2bp3的蛋白质，如果被禁用，会导致大多数斑马鱼发育为雄性。此外，少数能够进入成年期的雌性产生有缺陷的卵子，导致通常无法存活的异常后代。我们的工作确定了鱼类中决定正常发育和平衡性别比例的一个重要因素。Igf2bp3在其他动物中也有对应物，因此，我们的工作可以揭示这些过程如何在生物体中控制。
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, maternal igf2bp3 mutants exhibit reduced expression of germplasm transcripts, defects in chemokine guidance, abnormal PGC behavior and germ cell death. Consistently, adult igf2bp3 mutants 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. Animals develop from a single egg cell that is fertilised by sperm, to form various tissues and organs. How the different tissues form is still not fully understood. In particular, we don’t know precisely how organisms develop to be males or females, or how balanced sex ratios are maintained in populations. However, if these processes are disrupted, either too many males or too many females could arise in populations, which can lead to failure to produce the next generation, eventually resulting in extinction of the species. Therefore, identifying the factors that allow these processes to happen properly and deciphering how they function is crucial. We have identified a protein called Igf2bp3 in the tropical fish, Zebrafish, which if disabled, leads to most of the zebrafish developing as males. In addition, the few females that do make it to adulthood produce eggs that are defective, leading to abnormal progeny that generally do not survive. Our work identifies an important factor in fish that determines normal development and balanced sex ratios. Igf2bp3 has counterparts in other animals and therefore, our work can shed light on how these processes are controlled across organisms.
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