title: YAP/TAZ initiate and maintain Schwann cell myelination.
abstract: 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.
authors.affiliation: Shriners Hospitals Pediatric Research Center, Center for Neural Repair, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.|Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.
authors.forename: Matthew
authors.initials: M
authors.lastname: Grove
authors.affiliation: Shriners Hospitals Pediatric Research Center, Center for Neural Repair, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.|Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.
authors.forename: Hyukmin
authors.initials: H
authors.lastname: Kim
authors.affiliation: FELS Institute for Cancer Research and Molecular Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.
authors.forename: Maryline
authors.initials: M
authors.lastname: Santerre
authors.affiliation: Department of Bioengineering, Temple University, Philadelphia, United States.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Krupka
authors.affiliation: Shriners Hospitals Pediatric Research Center, Center for Neural Repair, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.|Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.
authors.forename: Seung Baek
authors.initials: SB
authors.lastname: Han
authors.affiliation: Shriners Hospitals Pediatric Research Center, Center for Neural Repair, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.|Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.
authors.forename: Jinbin
authors.initials: J
authors.lastname: Zhai
authors.affiliation: Shriners Hospitals Pediatric Research Center, Center for Neural Repair, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.
authors.forename: Jennifer Y
authors.initials: JY
authors.lastname: Cho
authors.affiliation: Shriners Hospitals Pediatric Research Center, Center for Neural Repair, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.|Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.
authors.forename: Raehee
authors.initials: R
authors.lastname: Park
authors.affiliation: Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.
authors.forename: Michele
authors.initials: M
authors.lastname: Harris
authors.affiliation: Shriners Hospitals Pediatric Research Center, Center for Neural Repair, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.|Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.
authors.forename: Seonhee
authors.initials: S
authors.lastname: Kim
authors.affiliation: FELS Institute for Cancer Research and Molecular Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.
authors.forename: Bassel E
authors.initials: BE
authors.lastname: Sawaya
authors.affiliation: Shriners Hospitals Pediatric Research Center, Center for Neural Repair, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.|Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.
authors.forename: Shin H
authors.initials: SH
authors.lastname: Kang
authors.affiliation: Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.
authors.forename: Mary F
authors.initials: MF
authors.lastname: Barbe
authors.affiliation: Shriners Hospitals Pediatric Research Center, Center for Neural Repair, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.|Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.
authors.forename: Seo-Hee
authors.initials: SH
authors.lastname: Cho
authors.affiliation: Department of Bioengineering, Temple University, Philadelphia, United States.
authors.forename: Michel A
authors.initials: MA
authors.lastname: Lemay
authors.affiliation: Shriners Hospitals Pediatric Research Center, Center for Neural Repair, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.|Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, United States.
authors.forename: Young-Jin
authors.identifier: 0000-0001-5725-9775
authors.initials: YJ
authors.lastname: Son
mesh_terms: D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D049109:Cell Proliferation; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D012583:Schwann Cells / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D000217:Acyltransferases; C486363:tafazzin protein, mouse
keywords: Egr2; Schwann cells; TEAD; Taz; demyelination; mouse; neuroscience