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在肌肉生成过程中，细胞质中的NOTCH和膜来源的β-连环蛋白将细胞命运选择与上皮-间质转化联系起来。

Cytoplasmic NOTCH and membrane-derived β-catenin link cell fate choice to epithelial-mesenchymal transition during myogenesis.

作者信息

Sieiro Daniel, Rios Anne C, Hirst Claire E, Marcelle Christophe

机构信息

Australian Regenerative Medicine Institute, Monash University, Clayton, Australia.

Institut NeuroMyoGene, University Lyon 1, CNRS UMR 5310, INSERM U 1217, Villeurbanne, France.

出版信息

Elife. 2016 May 24;5:e14847. doi: 10.7554/eLife.14847.

DOI:10.7554/eLife.14847
PMID:27218451
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4917337/
Abstract

How cells in the embryo coordinate epithelial plasticity with cell fate decision in a fast changing cellular environment is largely unknown. In chick embryos, skeletal muscle formation is initiated by migrating Delta1-expressing neural crest cells that trigger NOTCH signaling and myogenesis in selected epithelial somite progenitor cells, which rapidly translocate into the nascent muscle to differentiate. Here, we uncovered at the heart of this response a signaling module encompassing NOTCH, GSK-3β, SNAI1 and β-catenin. Independent of its transcriptional function, NOTCH profoundly inhibits GSK-3β activity. As a result SNAI1 is stabilized, triggering an epithelial to mesenchymal transition. This allows the recruitment of β-catenin from the membrane, which acts as a transcriptional co-factor to activate myogenesis, independently of WNT ligand. Our results intimately associate the initiation of myogenesis to a change in cell adhesion and may reveal a general principle for coupling cell fate changes to EMT in many developmental and pathological processes.

摘要

在快速变化的细胞环境中，胚胎中的细胞如何协调上皮可塑性与细胞命运决定，这在很大程度上尚不清楚。在鸡胚中，骨骼肌形成由迁移的表达Delta1的神经嵴细胞启动，这些细胞触发NOTCH信号并在选定的上皮体节祖细胞中诱导肌生成，这些祖细胞迅速转移到新生肌肉中进行分化。在这里，我们发现了这种反应的核心是一个包含NOTCH、GSK-3β、SNAI1和β-连环蛋白的信号模块。不依赖于其转录功能，NOTCH能显著抑制GSK-3β的活性。结果，SNAI1得以稳定，触发上皮-间充质转化。这使得β-连环蛋白从细胞膜上募集，β-连环蛋白作为转录辅因子激活肌生成，而不依赖于WNT配体。我们的结果将肌生成的起始与细胞黏附的变化紧密联系起来，并可能揭示了在许多发育和病理过程中将细胞命运变化与上皮-间充质转化相耦合的一般原则。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d89/4917337/32f9bd2a7eff/elife-14847-fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d89/4917337/202cc445f20e/elife-14847-fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d89/4917337/1b7c992b347c/elife-14847-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d89/4917337/5f2daabe7ea5/elife-14847-fig5-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d89/4917337/36a89205499f/elife-14847-fig6.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d89/4917337/2c644bdc1b36/elife-14847-fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d89/4917337/32f9bd2a7eff/elife-14847-fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d89/4917337/202cc445f20e/elife-14847-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d89/4917337/5e3511d2a197/elife-14847-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d89/4917337/639874db5e0c/elife-14847-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d89/4917337/7ce55e13eb60/elife-14847-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d89/4917337/4fca2059100f/elife-14847-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d89/4917337/e3be06a27612/elife-14847-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d89/4917337/1b7c992b347c/elife-14847-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d89/4917337/5f2daabe7ea5/elife-14847-fig5-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d89/4917337/36a89205499f/elife-14847-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d89/4917337/e4b742d524be/elife-14847-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d89/4917337/405d69d08875/elife-14847-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d89/4917337/2c644bdc1b36/elife-14847-fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d89/4917337/32f9bd2a7eff/elife-14847-fig10.jpg

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