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斑马鱼基因表达在神经发育过程中对 Mib1 介导的 Notch 信号的时空变化。

Temporal and Spatial Variations in Zebrafish Gene Expression in Response to Mib1-Mediated Notch Signaling During Neurodevelopment.

机构信息

Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan 333423, Taiwan.

Department of Neurology, Chang Gung Memorial Hospital at Linkou Medical Center, Taoyuan 333423, Taiwan.

出版信息

Int J Mol Sci. 2024 Aug 23;25(17):9174. doi: 10.3390/ijms25179174.

DOI:10.3390/ijms25179174
PMID:39273123
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11394890/
Abstract

Notch signaling is a conserved pathway crucial for nervous system development. Disruptions in this pathway are linked to neurodevelopmental disorders, neurodegenerative diseases, and brain tumors. genes, major downstream targets of Notch, are commonly used as markers for Notch activation. However, these genes can be activated, inhibited, or function independently of Notch signaling, and their response to Notch disruption varies across tissues and developmental stages. MIB1/Mib1 is an E3 ubiquitin ligase that enables Notch receptor activation by processing ligands like Delta and Serrate. We investigated Notch signaling disruption using the zebrafish Mib1 mutant line, , focusing on changes in the expression of () genes. Our findings reveal significant variability in gene expression across different neural cell types, regions, and developmental stages following Notch disruption. This variability questions the reliability of genes as universal markers for Notch activation, as their response is highly context-dependent. This study highlights the complex and context-specific nature of Notch signaling regulation. It underscores the need for a nuanced approach when using genes as markers for Notch activity. Additionally, it provides new insights into Mib1's role in Notch signaling, contributing to a better understanding of its involvement in Notch signaling-related disorders.

摘要

Notch 信号通路是神经系统发育过程中至关重要的保守途径。该通路的中断与神经发育障碍、神经退行性疾病和脑肿瘤有关。 Notch 的主要下游靶标 基因通常被用作 Notch 激活的标志物。然而，这些基因可以独立于 Notch 信号被激活、抑制或发挥功能，并且它们对 Notch 中断的反应在不同的组织和发育阶段有所不同。MIB1/Mib1 是一种 E3 泛素连接酶，通过加工 Delta 和 Serrate 等配体来促进 Notch 受体的激活。我们使用斑马鱼 Mib1 突变体系 研究了 Notch 信号中断，重点研究了 Notch 中断后不同神经细胞类型、区域和发育阶段 基因表达的变化。我们的研究结果表明， Notch 中断后，不同的神经细胞类型、区域和发育阶段的 基因表达存在显著的变异性。这种变异性质疑了 基因作为 Notch 激活的通用标志物的可靠性，因为它们的反应高度依赖于上下文。本研究强调了 Notch 信号调控的复杂性和上下文特异性。它突出了在将 基因用作 Notch 活性标志物时需要采取细致入微的方法。此外，它为 Mib1 在 Notch 信号中的作用提供了新的见解，有助于更好地理解其在 Notch 信号相关疾病中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e27/11394890/f23c2ac9371a/ijms-25-09174-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e27/11394890/748572b64246/ijms-25-09174-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e27/11394890/f23c2ac9371a/ijms-25-09174-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e27/11394890/748572b64246/ijms-25-09174-g001.jpg
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Cell Mol Neurobiol. 2023 Aug;43(6):2603-2620. doi: 10.1007/s10571-023-01340-w. Epub 2023 Apr 1.
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Notch signaling pathway: architecture, disease, and therapeutics.Notch 信号通路：结构、疾病与治疗。
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Multiple functions of Hes genes in the proliferation and differentiation of neural stem cells.Hes 基因在神经干细胞增殖和分化中的多重功能。
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