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Delta 样蛋白 1 胞内域通过 Notch 信号依赖性和非依赖性途径调控神经发育。

Cleaved Delta like 1 intracellular domain regulates neural development via Notch signal-dependent and -independent pathways.

机构信息

Division of Cellular and Molecular Toxicology, Center for Biological Safety & Research, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.

Institute for Advanced Life Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.

出版信息

Development. 2021 Oct 1;148(19). doi: 10.1242/dev.193664. Epub 2021 Oct 4.

DOI:10.1242/dev.193664
PMID:34519339
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8513606/
Abstract

Notch-Delta signaling regulates many developmental processes, including tissue homeostasis and maintenance of stem cells. Upon interaction of juxtaposed cells via Notch and Delta proteins, intracellular domains of both transmembrane proteins are cleaved and translocate to the nucleus. Notch intracellular domain activates target gene expression; however, the role of the Delta intracellular domain remains elusive. Here, we show the biological function of Delta like 1 intracellular domain (D1ICD) by modulating its production. We find that the sustained production of D1ICD abrogates cell proliferation but enhances neurogenesis in the developing dorsal root ganglia (DRG), whereas inhibition of D1ICD production promotes cell proliferation and gliogenesis. D1ICD acts as an integral component of lateral inhibition mechanism by inhibiting Notch activity. In addition, D1ICD promotes neurogenesis in a Notch signaling-independent manner. We show that D1ICD binds to Erk1/2 in neural crest stem cells and inhibits the phosphorylation of Erk1/2. In summary, our results indicate that D1ICD regulates DRG development by modulating not only Notch signaling but also the MAP kinase pathway.

摘要

Notch-Delta 信号通路调节许多发育过程，包括组织稳态和干细胞的维持。当相邻细胞通过 Notch 和 Delta 蛋白相互作用时，两种跨膜蛋白的细胞内结构域被切割并转移到细胞核中。Notch 细胞内结构域激活靶基因表达；然而，Delta 细胞内结构域的作用仍然难以捉摸。在这里，我们通过调节其产生来展示 Delta 样 1 细胞内结构域（D1ICD）的生物学功能。我们发现，D1ICD 的持续产生会破坏细胞增殖，但会增强发育中的背根神经节 (DRG) 中的神经发生，而抑制 D1ICD 的产生会促进细胞增殖和神经胶质发生。D1ICD 通过抑制 Notch 活性作为侧向抑制机制的组成部分。此外，D1ICD 以 Notch 信号通路独立的方式促进神经发生。我们表明 D1ICD 在神经嵴干细胞中与 Erk1/2 结合，并抑制 Erk1/2 的磷酸化。总之，我们的结果表明 D1ICD 通过调节不仅 Notch 信号通路而且还调节 MAP 激酶通路来调节 DRG 发育。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e5d/8513606/71d0c299893a/develop-148-193664-g8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e5d/8513606/8907e6f1dc1b/develop-148-193664-g6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e5d/8513606/4c2abb8e67e1/develop-148-193664-g7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e5d/8513606/71d0c299893a/develop-148-193664-g8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e5d/8513606/073c04c9c256/develop-148-193664-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e5d/8513606/bcf5e6d995ea/develop-148-193664-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e5d/8513606/1c6a6c922764/develop-148-193664-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e5d/8513606/508076c862c0/develop-148-193664-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e5d/8513606/fbd3534b97ca/develop-148-193664-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e5d/8513606/8907e6f1dc1b/develop-148-193664-g6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e5d/8513606/4c2abb8e67e1/develop-148-193664-g7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e5d/8513606/71d0c299893a/develop-148-193664-g8.jpg

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Dimethylsulfoxide Inhibits Oligodendrocyte Fate Choice of Adult Neural Stem and Progenitor Cells.二甲基亚砜抑制成年神经干细胞和祖细胞的少突胶质细胞命运选择。
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