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YAP/TAZ initiate and maintain schwann cell myelination
Grove, M Kim, H Santerre, M Krupka, AJ Han, SB Zhai, J Cho, JY Park, R Harris, M Kim, S
Grove, M
Kim, H
Santerre, M
Krupka, AJ
Han, SB
Zhai, J
Cho, JY
Park, R
Harris, M
Kim, S
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Journal Article
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2017-01-26
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10.7554/eLife.20982
Abstract
© Grove et al. 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.
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