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轴突依赖性 YAP/TAZ 表达介导施万细胞髓鞘再生，但不促进神经损伤后的增殖。

Axon-dependent expression of YAP/TAZ mediates Schwann cell remyelination but not proliferation after nerve injury.

机构信息

Shriners Hospitals Pediatric Research Center and Center for Neural Repair and Rehabilitation, Temple University, Philadelphia, United States.

Department of Anatomy and Cell Biology, Temple University, Philadelphia, United States.

出版信息

Elife. 2020 May 21;9:e50138. doi: 10.7554/eLife.50138.

DOI:10.7554/eLife.50138
PMID:32436841
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7259960/
Abstract

Previously we showed that YAP/TAZ promote not only proliferation but also differentiation of immature Schwann cells (SCs), thereby forming and maintaining the myelin sheath around peripheral axons (Grove et al., 2017). Here we show that YAP/TAZ are required for mature SCs to restore peripheral myelination, but not to proliferate, after nerve injury. We find that YAP/TAZ dramatically disappear from SCs of adult mice concurrent with axon degeneration after nerve injury. They reappear in SCs only if axons regenerate. YAP/TAZ ablation does not impair SC proliferation or transdifferentiation into growth promoting repair SCs. SCs lacking YAP/TAZ, however, fail to upregulate myelin-associated genes and completely fail to remyelinate regenerated axons. We also show that both YAP and TAZ are redundantly required for optimal remyelination. These findings suggest that axons regulate transcriptional activity of YAP/TAZ in adult SCs and that YAP/TAZ are essential for functional regeneration of peripheral nerve.

摘要

先前我们表明，YAP/TAZ 不仅促进未成熟雪旺细胞 (SCs) 的增殖，还促进其分化，从而形成并维持周围轴突的髓鞘 (Grove 等人，2017 年)。在这里，我们表明 YAP/TAZ 是成熟 SC 恢复周围髓鞘所必需的，但在神经损伤后不会增殖。我们发现，YAP/TAZ 在神经损伤后轴突退化时，从成年小鼠的 SC 中急剧消失。只有轴突再生时，它们才会重新出现在 SC 中。YAP/TAZ 缺失不会损害 SC 的增殖或向促进生长的修复 SC 的转分化。然而，缺乏 YAP/TAZ 的 SC 无法上调髓鞘相关基因，并且完全无法对再生轴突进行髓鞘再形成。我们还表明，YAP 和 TAZ 对于最佳髓鞘再形成都是冗余必需的。这些发现表明，轴突调节成年 SC 中 YAP/TAZ 的转录活性，并且 YAP/TAZ 对于周围神经的功能再生是必不可少的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/d424f9cc7704/elife-50138-fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/d533287a9839/elife-50138-fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/4ca6c8ca7a6d/elife-50138-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/8b671aa2e3fc/elife-50138-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/cc34a564c916/elife-50138-fig4.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/7eaec2b55df9/elife-50138-fig7-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/d10895468335/elife-50138-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/b2d3364963b0/elife-50138-fig8-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/d424f9cc7704/elife-50138-fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/d533287a9839/elife-50138-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/3497dae76c96/elife-50138-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/6e968006afe0/elife-50138-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/4ca6c8ca7a6d/elife-50138-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/8b671aa2e3fc/elife-50138-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/cc34a564c916/elife-50138-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/446e64714408/elife-50138-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/ff1e5cd9eae2/elife-50138-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/71313ef2d440/elife-50138-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/1d984552644e/elife-50138-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/7eaec2b55df9/elife-50138-fig7-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/d10895468335/elife-50138-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/b2d3364963b0/elife-50138-fig8-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97d/7259960/d424f9cc7704/elife-50138-fig9.jpg

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