Liu Zhe, Wang Wei, Li Xinru, Zhao Xiujuan, Zhao Hongyu, Yang Wuritu, Zuo Yongchun, Cai Lu, Xing Yongqiang
The Inner Mongolia Key Laboratory of Functional Genome Bioinformatics, School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, China.
State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, China.
Front Cell Dev Biol. 2022 Jul 8;10:879795. doi: 10.3389/fcell.2022.879795. eCollection 2022.
Alternative splicing is pervasive in mammalian genomes and involved in embryo development, whereas research on crosstalk of alternative splicing and embryo development was largely restricted to mouse and human and the alternative splicing regulation during embryogenesis in zebrafish remained unclear. We constructed the alternative splicing atlas at 18 time-course stages covering maternal-to-zygotic transition, gastrulation, somitogenesis, pharyngula stages, and post-fertilization in zebrafish. The differential alternative splicing events between different developmental stages were detected. The results indicated that abundance alternative splicing and differential alternative splicing events are dynamically changed and remarkably abundant during the maternal-to-zygotic transition process. Based on gene expression profiles, we found splicing factors are expressed with specificity of developmental stage and largely expressed during the maternal-to-zygotic transition process. The better performance of cluster analysis was achieved based on the inclusion level of alternative splicing. The biological function analysis uncovered the important roles of alternative splicing during embryogenesis. The identification of isoform switches of alternative splicing provided a new insight into mining the regulated mechanism of transcript isoforms, which always is hidden by gene expression. In conclusion, we inferred that alternative splicing activation is synchronized with zygotic genome activation and discovered that alternative splicing is coupled with transcription during embryo development in zebrafish. We also unveiled that the temporal expression dynamics of splicing factors during embryo development, especially co-orthologous splicing factors. Furthermore, we proposed that the inclusion level of alternative splicing events can be employed for cluster analysis as a novel parameter. This work will provide a deeper insight into the regulation of alternative splicing during embryogenesis in zebrafish.
可变剪接在哺乳动物基因组中普遍存在，并参与胚胎发育，然而，关于可变剪接与胚胎发育相互作用的研究主要局限于小鼠和人类，斑马鱼胚胎发育过程中的可变剪接调控仍不清楚。我们构建了斑马鱼从母源到合子转变、原肠胚形成、体节发生、咽胚期以及受精后的18个时间进程阶段的可变剪接图谱。检测了不同发育阶段之间的差异可变剪接事件。结果表明，在母源到合子转变过程中，丰富的可变剪接和差异可变剪接事件动态变化且显著丰富。基于基因表达谱，我们发现剪接因子在发育阶段具有特异性表达，并且在母源到合子转变过程中大量表达。基于可变剪接的包含水平，聚类分析表现更佳。生物学功能分析揭示了可变剪接在胚胎发生过程中的重要作用。可变剪接异构体开关的鉴定为挖掘转录异构体的调控机制提供了新的视角，而转录异构体的调控机制往往被基因表达所掩盖。总之，我们推断可变剪接激活与合子基因组激活同步，并发现斑马鱼胚胎发育过程中可变剪接与转录偶联。我们还揭示了胚胎发育过程中剪接因子的时间表达动态，尤其是共直系剪接因子。此外，我们提出可变剪接事件的包含水平可作为一个新参数用于聚类分析。这项工作将为深入了解斑马鱼胚胎发生过程中可变剪接的调控提供帮助。
