YAP/TAZ initiate and maintain Schwann cell myelination

被引：68

作者：

Grove, Matthew ^{[1
,2
]}

Kim, Hyukmin ^{[1
,2
]}

Santerre, Maryline ^{[3
]}

Krupka, Alexander J. ^{[4
]}

Han, Seung Baek ^{[1
,2
]}

Zhai, Jinbin ^{[1
,2
]}

Cho, Jennifer Y. ^{[1
]}

Park, Raehee ^{[1
,2
]}

Harris, Michele ^{[2
]}

Kim, Seonhee ^{[1
,2
]}

Sawaya, Bassel E. ^{[3
]}

Kang, Shin H. ^{[1
,2
]}

Barbe, Mary F. ^{[2
]}

Cho, Seo-Hee ^{[1
,2
]}

Lemay, Michel A. ^{[4
]}

Son, Young-Jin ^{[1
,2
]}

机构：

[1] Temple Univ, Shriners Hosp Pediat Res Ctr, Ctr Neural Repair, Lewis Katz Sch Med, Philadelphia, PA 19122 USA

[2] Temple Univ, Dept Anat & Cell Biol, Lewis Katz Sch Med, Philadelphia, PA 19122 USA

[3] Temple Univ, Lewis Katz Sch Med, FELS Inst Canc Res & Mol Biol, Philadelphia, PA 19122 USA

[4] Temple Univ, Dept Bioengn, Philadelphia, PA 19122 USA

来源：

ELIFE | 2017年 / 6卷

关键词：

PERIPHERAL NERVOUS-SYSTEM; HIPPO PATHWAY; TUMOR-SUPPRESSOR; GENE-EXPRESSION; TRANSGENIC MICE; YAP; DIFFERENTIATION; AXONS; TAZ; CANCER;

D O I：

10.7554/eLife.20982

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Nuclear exclusion of the transcriptional regulators and potent oncoproteins, YAP/TAZ, is considered necessary for adult tissue homeostasis. Here we show that nuclear YAP/TAZ are essential regulators of peripheral nerve development and myelin maintenance. To proliferate, developing Schwann cells (SCs) require YAP/TAZ to enter S-phase and, without them, fail to generate sufficient SCs for timely axon sorting. To differentiate, SCs require YAP/TAZ to upregulate Krox20 and, without them, completely fail to myelinate, resulting in severe peripheral neuropathy. Remarkably, in adulthood, nuclear YAP/TAZ are selectively expressed by myelinating SCs, and conditional ablation results in severe peripheral demyelination and mouse death. YAP/TAZ regulate both developmental and adult myelination by driving TEAD1 to activate Krox20. Therefore, YAP/TAZ are crucial for SCs to myelinate developing nerve and to maintain myelinated nerve in adulthood. Our study also provides a new insight into the role of nuclear YAP/TAZ in homeostatic maintenance of an adult tissue.

引用

页数：27

共 74 条

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