TEAD1 is crucial for myelination, Remak bundles and functional regeneration of peripheral nerves

The hippo pathway transcriptional effectors, YAP/TAZ, are crucial for Schwann cells (SCs) to myelinate axons but the partner transcription factor remains undetermined. Here, using conditional and inducible knockout mice, we report that TEAD1 is essential for SCs to develop, grow, and regenerate myelin sheaths. TEAD1/2/3/4 are all present in SCs, but YAP/TAZ strongly favors TEAD1. It promotes myelination by both positively and negatively regulating SC proliferation, enabling Krox20/Egr2 to upregulate myelin proteins, and upregulating the cholesterol biosynthetic enzymes FDPS and IDI1. We also show stage-dependent redundancy of TEAD1 and that non-myelinating SCs have a unique requirement for TEAD1 to enwrap nociceptive axons in Remak bundles. Our findings establish TEAD1 as a crucial partner of YAP/TAZ in developmental myelination and functional nerve regeneration and as a novel transcription factor regulating Remak bundle integrity.