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功能表征与表达分析揭示母源和合子型Dgcr8在早期胚胎发育中的不同作用。

Functional Characterization and Expression Analyses Show Differential Roles of Maternal and Zygotic Dgcr8 in Early Embryonic Development.

作者信息

Zhu Zeyao, Liu Yun, Xu Wen, Liu Taian, Xie Yuxin, Sham Kathy W Y, Sha Ou, Cheng Christopher H K

机构信息

Department of Anatomy, Histology and Developmental Biology, School of Basic Medical Sciences, Shenzhen University, Shenzhen, China.

School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.

出版信息

Front Genet. 2020 Mar 31;11:299. doi: 10.3389/fgene.2020.00299. eCollection 2020.

Abstract

Dgcr8 is involved in the biogenesis of canonical miRNAs to process pri-miRNA into pre-miRNA. Previous studies have provided evidence that Dgcr8 plays an essential role in different biological processes. However, the function of maternal and zygotic Dgcr8 in early embryonic development remains largely unknown. Recently, we have reported a novel approach for generating germline-specific deletions in zebrafish. This germline knockout model offers an opportunity to investigate into the differential roles of maternal or zygotic Dgcr8. Although germline specific dgcr8 deletion has no influence on gonad development, maternal or zygotic dgcr8 is essential for embryonic development in the offspring. Both maternal (M) and maternal zygotic (MZ) mutants display multiple developmental defects and die within 1 week. Moreover, MZ mutant displays more severe morphogenesis defects. However, when a miR-430 duplex (the most abundantly expressed miRNA in early embryonic stage) is used to rescue the maternal mutant phenotype, the Mdgcr8 embryos could be rescued successfully and grow into adulthood and achieve sexual maturation, whereas the MZ embryos are only partially rescued and they all die within 1 week. The differential phenotypes between the Mdgcr8 and MZ embryos provide us with an opportunity to study the roles of individual miRNAs during early development.

摘要

Dgcr8参与经典微小RNA(miRNA)的生物合成,将初级miRNA(pri-miRNA)加工成前体miRNA(pre-miRNA)。先前的研究已提供证据表明Dgcr8在不同的生物学过程中起重要作用。然而,母源和合子源Dgcr8在早期胚胎发育中的功能仍 largely未知。最近,我们报道了一种在斑马鱼中产生生殖系特异性缺失的新方法。这种生殖系敲除模型为研究母源或合子源Dgcr8的不同作用提供了一个机会。虽然生殖系特异性dgcr8缺失对性腺发育没有影响,但母源或合子源dgcr8对后代的胚胎发育至关重要。母源(M)突变体和合子母源(MZ)突变体均表现出多种发育缺陷,并在1周内死亡。此外,MZ突变体表现出更严重的形态发生缺陷。然而,当使用miR-430双链体(早期胚胎阶段表达最丰富的miRNA)来挽救母源突变体表型时,Mdgcr8胚胎能够成功获救并成长至成年并实现性成熟,而MZ胚胎仅部分获救,它们都在1周内死亡。Mdgcr8胚胎和MZ胚胎之间的不同表型为我们提供了一个研究早期发育过程中单个miRNA作用的机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5542/7136893/aa0bd37bd455/fgene-11-00299-g001.jpg

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