Department of Life Science, BK21 Plus Program, Graduate School, Chungnam National University, Daejeon 34134, South Korea.
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 3354, Saudi Arabia.
Gene. 2019 Apr 30;694:1-6. doi: 10.1016/j.gene.2018.12.078. Epub 2019 Feb 1.
Pellino proteins are associated with immune and stress responses through their effects on NF-κB signaling and B-cell development, and through their role as a scaffold in TLR/IL-1R signaling pathways. However, their function during embryonic development is unclear. Here, we report the developmental expression patterns and functions of peli1b, which encodes a zebrafish ortholog of human Pellino1. Maternal peli1b transcripts were present in zebrafish embryos at the 1-cell stage and zygotic transcripts appeared in the shield area at 6 hours post fertilization (hpf), particularly in the neural plate of the dorsal region. peli1b transcripts were concentrated in the somites, lens, myogenic cells, lateral plate mesoderm, and presomitic mesoderm at 12 hpf, but expression shifted to the telencephalon, diencephalon, hindbrain, and rhombomeres (r1-7) at 24 hpf. Distribution of peli1b transcripts was further restricted to the telencephalon, diencephalon, hindbrain, eyes, and pectoral fins at 48 hpf. Knock-down of peli1b with a peli1b antisense morpholino resulted in significant developmental defects and a reduction in size of the telencephalon, diencephalon, rhombomeres (r1-7), and spinal cord at 24 hpf. When peli1b-knock-down embryos were analyzed for zic3, a marker associated with the central nervous system, we found lower levels of zic3 transcripts in the shield area at 6 hpf and in the posterior diencephalon, dorsal neural plate, midbrain, and hindbrain at 14 hpf. Finally, the ERK3/4 inhibitor SB203580 also induced a significant reduction in the level of zic3 transcripts in the neural plate at 6 hpf and in the posterior diencephalon, dorsal neural plate, midbrain, hindbrain, segmental plate, dorsal spinal cord, and dorsal posterior neural plate at 14 hpf. It is thus likely that the association between Peli1b and brain development in zebrafish embryos occurs via ERK3/4 pathways.
Pellino 蛋白通过影响 NF-κB 信号和 B 细胞发育，以及作为 TLR/IL-1R 信号通路的支架，参与免疫和应激反应。然而，它们在胚胎发育过程中的功能尚不清楚。在这里，我们报告了 peli1b 的发育表达模式和功能，peli1b 编码斑马鱼与人 Pellino1 的同源物。母源 peli1b 转录本在斑马鱼胚胎的 1 细胞期存在，合子转录本在受精后 6 小时（hpf）出现在盾区，特别是在背部神经板中。peli1b 转录本在 12 hpf 时集中在体节、晶状体、肌细胞、侧板中胚层和前体节中胚层，但在 24 hpf 时表达转移到端脑、间脑、后脑和菱脑节（r1-7）。在 48 hpf 时，peli1b 转录本的分布进一步局限于端脑、间脑、后脑、眼睛和胸鳍。用 peli1b 反义 morpholino 敲低 peli1b 导致 24 hpf 时端脑、间脑、菱脑节（r1-7）和脊髓的发育缺陷和大小减小。当分析 peli1b 敲低胚胎中的 zic3（与中枢神经系统相关的标志物）时，我们发现 6 hpf 时在盾区和 14 hpf 时在后间脑、背侧神经板、中脑和后脑中 zic3 转录本水平较低。最后，ERK3/4 抑制剂 SB203580 也在 6 hpf 时的神经板和 14 hpf 时的后间脑、背侧神经板、中脑、后脑、节段板、背侧脊髓和背侧后神经板中诱导 zic3 转录本水平的显著降低。因此，Peli1b 与斑马鱼胚胎大脑发育之间的关联可能通过 ERK3/4 途径发生。
