Zebrafish PEX1 Is Required for the Generation of GABAergic Neuron in p3 Domain.

Development & reproduction Pub Date : 2024-12-01 Epub Date: 2024-12-31 DOI:10.12717/DR.2024.28.4.129
Jae-Ho Ryu, Minjung Kim, Aseung Kim, Hyunju Ro, Seok-Hyung Kim, Sang-Yeob Yeo
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Abstract

Maintenance of neural progenitors requires Notch signaling in vertebrate development. Previous study has shown that Jagged2-mediated Notch signaling maintains proliferating neural progenitors in the ventral spinal cord. However, components for Jagged-mediated signaling remain poorly defined during late neurogenesis. Here we performed yeast-two hybrid screening by using the intracellular domain (ICD) of zebrafish Jagged2, and investigated a possible role of PEX1 as a component of Notch signaling for the cell-fate decision and the differentiation of neural precursors in p3 domain. Western blotting showed that zebrafish PEX1 might interacts with the ICD of zebrafish Jagged2 physically. PEX1 morpholino-injected embryos showed the increased number of GABAergic KA" neurons as well as the ectopic expression of secondary motor neurons in the p3 domain. The increased number of KA" neurons was also observed in the zebrafish embryos with PEX1 mutation induced by CRISPR/Cas9. These phenotypes resemble with that of Jagged2 morphant. Our observations imply that a critical role of PEX1 in the cell-fate decision of proliferating neural precursors in the p3 domain during the continuing growth and development of the vertebrate nervous system.

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斑马鱼p3区域gaba能神经元的生成需要PEX1。
在脊椎动物发育过程中,神经祖细胞的维持需要Notch信号。先前的研究表明,jagged2介导的Notch信号可以维持脊髓腹侧神经祖细胞的增殖。然而,在神经发生晚期,锯齿状介导的信号的组成部分仍然不明确。本研究利用斑马鱼Jagged2的胞内结构域(ICD)进行了酵母- 2杂交筛选,并研究了PEX1作为Notch信号的一个组成部分在细胞命运决定和p3结构域神经前体分化中的可能作用。Western blotting表明斑马鱼PEX1可能与斑马鱼Jagged2的ICD发生物理相互作用。注射PEX1 morpholinos的胚胎显示gaba能KA"神经元数量增加,p3区域次级运动神经元异位表达。在CRISPR/Cas9诱导的PEX1突变的斑马鱼胚胎中也观察到KA”神经元数量的增加。这些表型与Jagged2突变体相似。我们的观察结果表明,在脊椎动物神经系统的持续生长和发育过程中,PEX1在增殖神经前体p3结构域的细胞命运决定中起着关键作用。
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