• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

在斑马鱼胚胎细胞中的化学筛选确定 Akt 激活对于神经嵴发育是必需的。

A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest development.

机构信息

Stem Cell Program and Hematology/Oncology, Children's Hospital Boston, Howard Hughes Medical Institute, Boston, United States.

Harvard Medical School, Boston, United States.

出版信息

Elife. 2017 Aug 23;6:e29145. doi: 10.7554/eLife.29145.

DOI:10.7554/eLife.29145
PMID:28832322
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5599238/
Abstract

The neural crest is a dynamic progenitor cell population that arises at the border of neural and non-neural ectoderm. The inductive roles of FGF, Wnt, and BMP at the neural plate border are well established, but the signals required for subsequent neural crest development remain poorly characterized. Here, we conducted a screen in primary zebrafish embryo cultures for chemicals that disrupt neural crest development, as read out by expression. We found that the natural product caffeic acid phenethyl ester (CAPE) disrupts neural crest gene expression, migration, and melanocytic differentiation by reducing Sox10 activity. CAPE inhibits FGF-stimulated PI3K/Akt signaling, and neural crest defects in CAPE-treated embryos are suppressed by constitutively active Akt1. Inhibition of Akt activity by constitutively active PTEN similarly decreases expression and Sox10 activity. Our study has identified Akt as a novel intracellular pathway required for neural crest differentiation.

摘要

神经嵴是一种起源于神经和非神经外胚层交界处的动态祖细胞群体。神经板边界处 FGF、Wnt 和 BMP 的诱导作用已得到充分证实，但随后神经嵴发育所需的信号仍知之甚少。在这里，我们在原代斑马鱼胚胎培养物中进行了一项筛选，以寻找通过 表达读出的破坏神经嵴发育的化学物质。我们发现，天然产物咖啡酸苯乙酯 (CAPE) 通过降低 Sox10 活性来破坏神经嵴基因表达、迁移和黑素细胞分化。CAPE 抑制 FGF 刺激的 PI3K/Akt 信号转导，并且 CAPE 处理的胚胎中的神经嵴缺陷可被组成型活性 Akt1 抑制。通过组成型活性 PTEN 抑制 Akt 活性同样会降低 表达和 Sox10 活性。我们的研究已经确定 Akt 是神经嵴分化所必需的新的细胞内途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/25b36e95e88d/elife-29145-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/f47807bfcee3/elife-29145-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/f344e5309baf/elife-29145-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/0708345bd8a1/elife-29145-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/0081eaf26fa8/elife-29145-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/7a88e41f41b8/elife-29145-fig2-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/fece1dd03751/elife-29145-fig2-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/ccca8ba3b97c/elife-29145-fig2-figsupp4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/4cc44d5820bd/elife-29145-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/fbce048236ab/elife-29145-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/9c0ec4233fef/elife-29145-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/e3fe0f3b7f3d/elife-29145-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/f13348c92080/elife-29145-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/8a1e8a31c76b/elife-29145-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/7e1bab34f662/elife-29145-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/18575f73dbd5/elife-29145-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/6e28d434a8a9/elife-29145-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/815bff663195/elife-29145-fig6-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/25b36e95e88d/elife-29145-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/f47807bfcee3/elife-29145-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/f344e5309baf/elife-29145-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/0708345bd8a1/elife-29145-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/0081eaf26fa8/elife-29145-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/7a88e41f41b8/elife-29145-fig2-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/fece1dd03751/elife-29145-fig2-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/ccca8ba3b97c/elife-29145-fig2-figsupp4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/4cc44d5820bd/elife-29145-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/fbce048236ab/elife-29145-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/9c0ec4233fef/elife-29145-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/e3fe0f3b7f3d/elife-29145-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/f13348c92080/elife-29145-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/8a1e8a31c76b/elife-29145-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/7e1bab34f662/elife-29145-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/18575f73dbd5/elife-29145-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/6e28d434a8a9/elife-29145-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/815bff663195/elife-29145-fig6-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f0/5599238/25b36e95e88d/elife-29145-fig7.jpg

相似文献

1
A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest development.在斑马鱼胚胎细胞中的化学筛选确定 Akt 激活对于神经嵴发育是必需的。
Elife. 2017 Aug 23;6:e29145. doi: 10.7554/eLife.29145.
2
AKT signaling displays multifaceted functions in neural crest development.AKT信号通路在神经嵴发育中发挥多方面的功能。
Dev Biol. 2018 Dec 1;444 Suppl 1:S144-S155. doi: 10.1016/j.ydbio.2018.05.023. Epub 2018 May 31.
3
Tfap2a and Foxd3 regulate early steps in the development of the neural crest progenitor population.Tfap2a 和 Foxd3 调节神经嵴祖细胞群体发育的早期步骤。
Dev Biol. 2011 Dec 1;360(1):173-85. doi: 10.1016/j.ydbio.2011.09.019. Epub 2011 Sep 22.
4
SNW1 is a critical regulator of spatial BMP activity, neural plate border formation, and neural crest specification in vertebrate embryos.SNW1 是脊椎动物胚胎中空间 BMP 活性、神经板边界形成和神经嵴特化的关键调节因子。
PLoS Biol. 2011 Feb 15;9(2):e1000593. doi: 10.1371/journal.pbio.1000593.
5
Posteriorization by FGF, Wnt, and retinoic acid is required for neural crest induction.神经嵴诱导需要FGF、Wnt和视黄酸进行后化。
Dev Biol. 2002 Jan 15;241(2):289-301. doi: 10.1006/dbio.2001.0485.
6
Specific pan-neural crest expression of zebrafish Crestin throughout embryonic development.斑马鱼Crestin在整个胚胎发育过程中的特异性泛神经嵴表达。
Dev Dyn. 2001 Feb;220(2):169-74. doi: 10.1002/1097-0177(2000)9999:9999<::AID-DVDY1097>3.0.CO;2-1.
7
Zebrafish arl6ip1 is required for neural crest development during embryogenesis.斑马鱼 arl6ip1 对于胚胎发生过程中的神经嵴发育是必需的。
PLoS One. 2012;7(3):e32899. doi: 10.1371/journal.pone.0032899. Epub 2012 Mar 9.
8
Caffeic acid phenethyl ester attenuates lipopolysaccharide-stimulated proinflammatory responses in human gingival fibroblasts via NF-κB and PI3K/Akt signaling pathway.阿魏酸苯乙酯通过 NF-κB 和 PI3K/Akt 信号通路减轻脂多糖刺激的人牙龈成纤维细胞的促炎反应。
Eur J Pharmacol. 2017 Jan 5;794:61-68. doi: 10.1016/j.ejphar.2016.11.003. Epub 2016 Nov 7.
9
Ectodermal Wnt function as a neural crest inducer.外胚层Wnt作为一种神经嵴诱导因子发挥作用。
Science. 2002 Aug 2;297(5582):848-51. doi: 10.1126/science.1070824.
10
Caffeic Acid Phenethyl Ester (CAPE) Protects PC12 Cells Against Cisplatin-Induced Neurotoxicity by Activating the AMPK/SIRT1, MAPK/Erk, and PI3k/Akt Signaling Pathways.绿原酸苯乙酯（CAPE）通过激活 AMPK/SIRT1、MAPK/Erk 和 PI3k/Akt 信号通路来保护 PC12 细胞免受顺铂诱导的神经毒性。
Neurotox Res. 2019 Jul;36(1):175-192. doi: 10.1007/s12640-019-00042-w. Epub 2019 Apr 23.

引用本文的文献

1
Dis3l2 is essential for neural crest survival by modulating Akt signaling.Dis3l2通过调节Akt信号通路对神经嵴细胞的存活至关重要。
Cell Commun Signal. 2025 Jun 11;23(1):277. doi: 10.1186/s12964-025-02288-8.
2
The Role of the Sirtuin Family Histone Deacetylases in Acute Myeloid Leukemia-A Promising Road Ahead.沉默调节蛋白家族组蛋白去乙酰化酶在急性髓系白血病中的作用——前路光明。
Cancers (Basel). 2025 Mar 17;17(6):1009. doi: 10.3390/cancers17061009.
3
Construction of tissue engineered cornea with skin-derived corneal endothelial-like cell and mechanism research for the cell differentiation.

本文引用的文献

1
Sox10 contributes to the balance of fate choice in dorsal root ganglion progenitors.Sox10有助于维持背根神经节祖细胞命运选择的平衡。
PLoS One. 2017 Mar 2;12(3):e0172947. doi: 10.1371/journal.pone.0172947. eCollection 2017.
2
Embryonic cell culture in zebrafish.斑马鱼的胚胎细胞培养
Methods Cell Biol. 2016;133:1-10. doi: 10.1016/bs.mcb.2016.02.010. Epub 2016 Mar 31.
3
Leader Cells Define Directionality of Trunk, but Not Cranial, Neural Crest Cell Migration.引导细胞决定躯干而非头部神经嵴细胞迁移的方向性。
皮肤源角膜内皮样细胞构建组织工程角膜及细胞分化机制研究
Front Med (Lausanne). 2024 Sep 2;11:1448248. doi: 10.3389/fmed.2024.1448248. eCollection 2024.
4
Deciphering the enigma of the function of alpha-tocopherol as a vitamin.解析α-生育酚作为维生素功能的奥秘。
Free Radic Biol Med. 2024 Aug 20;221:64-74. doi: 10.1016/j.freeradbiomed.2024.05.028. Epub 2024 May 15.
5
The interplay of common genetic variants NRG1 rs2439302 and RET rs2435357 increases the risk of developing Hirschsprung's disease.常见基因变异NRG1 rs2439302和RET rs2435357的相互作用会增加患先天性巨结肠症的风险。
Front Cell Dev Biol. 2023 Jul 7;11:1184799. doi: 10.3389/fcell.2023.1184799. eCollection 2023.
6
Multiple congenital malformations arise from somatic mosaicism for constitutively active Pik3ca signaling.多种先天性畸形源于组成型激活的Pik3ca信号传导的体细胞镶嵌现象。
Front Cell Dev Biol. 2022 Oct 24;10:1013001. doi: 10.3389/fcell.2022.1013001. eCollection 2022.
7
Glucocorticoid receptor activation reduces food intake independent of hyperglycemia in zebrafish.糖皮质激素受体激活可减少斑马鱼的摄食量，与高血糖无关。
Sci Rep. 2022 Sep 20;12(1):15677. doi: 10.1038/s41598-022-19572-z.
8
Review: The Role of Wnt/β-Catenin Signalling in Neural Crest Development in Zebrafish.综述：Wnt/β-连环蛋白信号通路在斑马鱼神经嵴发育中的作用
Front Cell Dev Biol. 2021 Nov 29;9:782445. doi: 10.3389/fcell.2021.782445. eCollection 2021.
9
Zebrafish disease models in drug discovery: from preclinical modelling to clinical trials.斑马鱼疾病模型在药物研发中的应用：从临床前建模到临床试验。
Nat Rev Drug Discov. 2021 Aug;20(8):611-628. doi: 10.1038/s41573-021-00210-8. Epub 2021 Jun 11.
10
Functional in vivo characterization of sox10 enhancers in neural crest and melanoma development.体内功能分析 Sox10 增强子在神经嵴和黑色素瘤发育中的作用。
Commun Biol. 2021 Jun 7;4(1):695. doi: 10.1038/s42003-021-02211-0.
Cell Rep. 2016 May 31;15(9):2076-88. doi: 10.1016/j.celrep.2016.04.067. Epub 2016 May 19.
4
Fine-Tuning of Pten Localization and Phosphatase Activity Is Essential for Zebrafish Angiogenesis.Pten定位和磷酸酶活性的微调对斑马鱼血管生成至关重要。
PLoS One. 2016 May 3;11(5):e0154771. doi: 10.1371/journal.pone.0154771. eCollection 2016.
5
A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation.斑马鱼黑色素瘤模型揭示了黑色素瘤起始过程中神经嵴特征的出现。
Science. 2016 Jan 29;351(6272):aad2197. doi: 10.1126/science.aad2197. Epub 2016 Jan 28.
6
Neural crest migration is driven by a few trailblazer cells with a unique molecular signature narrowly confined to the invasive front.神经嵴迁移由少数具有独特分子特征的先驱细胞驱动，这些细胞严格局限于侵袭前沿。
Development. 2015 Jun 1;142(11):2014-25. doi: 10.1242/dev.117507. Epub 2015 May 14.
7
PFKFB4 controls embryonic patterning via Akt signalling independently of glycolysis.PFKFB4 通过 Akt 信号通路独立于糖酵解控制胚胎模式形成。
Nat Commun. 2015 Jan 20;6:5953. doi: 10.1038/ncomms6953.
8
Leader cells regulate collective cell migration via Rac activation in the downstream signaling of integrin β1 and PI3K.引导细胞通过整合素β1和PI3K下游信号通路中的Rac激活来调节集体细胞迁移。
Sci Rep. 2015 Jan 7;5:7656. doi: 10.1038/srep07656.
9
Characterization of cultured multipotent zebrafish neural crest cells.培养的多能斑马鱼神经嵴细胞的特征。
Exp Biol Med (Maywood). 2014 Feb;239(2):159-68. doi: 10.1177/1535370213513997. Epub 2013 Dec 10.
10
Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position.天然染色质易位用于快速灵敏的染色质开放性、DNA 结合蛋白和核小体位置的表观基因组分析。
Nat Methods. 2013 Dec;10(12):1213-8. doi: 10.1038/nmeth.2688. Epub 2013 Oct 6.