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发育中的斑马鱼头的整合mRNA和miRNA表达谱突出了脑偏好基因和调控网络。

Integrative mRNA and miRNA Expression Profiles from Developing Zebrafish Head Highlight Brain-Preference Genes and Regulatory Networks.

作者信息

Zhang Shuqiang, Yang Jian, Xu Jie, Li Jing, Xu Lian, Jin Nana, Li Xiaoyu

机构信息

College of Life Science, Henan Normal University, Xinxiang, 453007, Henan, China.

Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Researchand, Evaluation of Tissue Engineering Technology Products , Nantong University, Nantong, 226001, China.

出版信息

Mol Neurobiol. 2025 Feb;62(2):2148-2162. doi: 10.1007/s12035-024-04364-5. Epub 2024 Jul 31.

Abstract

Zebrafish is an emerging animal model for studying molecular mechanism underlying neurodevelopmental disorder due to its advantage characters. miRNAs are small non-coding RNAs that play a key role in brain development. Understanding of dynamic transcriptional and post-transcriptional molecules and their regulation during the head development is important for the study of neurodevelopmental disorder. In this study, we performed the high-throughput sequencing of mRNAs and miRNAs in developing zebrafish head from pharyngula to early larval stages and carried out bioinformatic analysis including differential expression and functional enrichment as well as joint analysis of miRNAs and mRNAs, and also compared with other related public sequencing datasets to aid our interpretation. A large number of differential expression genes with a large fold change were detected during the head development. Further clustering and functional enrichment analyses indicated that genes in late stage were most related with synaptic signaling. Overlap test analysis showed a significant enrichment of brain-preference and synapse-associated gene set in the head transcriptome compared with the whole embryo transcriptome. We also constructed miRNA-mRNA network for those brain-preference genes and focused on those densely connected network components. CRISPR-Cas9-mediated snap25b mutants led to embryonic development defects and decreases locomotor activity. Altogether, the present study provides developmental profiles of head-enriched mRNAs and miRNAs at three critical windows for nervous system development, which may contribute to the study of neurodevelopmental disorder.

摘要

斑马鱼因其优势特性,成为研究神经发育障碍潜在分子机制的新兴动物模型。微小RNA(miRNAs)是一类在大脑发育中起关键作用的小非编码RNA。了解头部发育过程中动态的转录和转录后分子及其调控,对于神经发育障碍的研究至关重要。在本研究中,我们对从咽胚期到幼体早期发育阶段的斑马鱼头部进行了mRNA和miRNA的高通量测序,并进行了生物信息学分析,包括差异表达、功能富集以及miRNA和mRNA的联合分析,还与其他相关的公共测序数据集进行比较以辅助我们的解读。在头部发育过程中检测到大量具有大倍数变化的差异表达基因。进一步的聚类和功能富集分析表明,晚期基因与突触信号传导最为相关。重叠测试分析显示,与全胚胎转录组相比,头部转录组中脑偏好和突触相关基因集显著富集。我们还构建了这些脑偏好基因的miRNA-mRNA网络,并关注那些连接紧密的网络组件。CRISPR-Cas9介导的snap25b突变体导致胚胎发育缺陷和运动活性降低。总之,本研究提供了神经系统发育三个关键窗口中头部富集的mRNA和miRNA的发育图谱,这可能有助于神经发育障碍的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c2a/11772381/7903f4fcaa46/12035_2024_4364_Fig1_HTML.jpg

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