Transcription Factors and Coregulators in Schwann Cell Differentiation, Myelination, and Remyelination: Implications for Peripheral Neuropathy

Schwann cells (SCs) are required for supporting axons, forming myelin, and facilitating repair through remyelination after injury in the peripheral nervous system (PNS). Processes of differentiation, myelination, and remyelination of SCs are tightly modulated by a complex network of transcription factors and coregulators, including Sox10, Oct6/Pou3f1, Krox20/Egr2, Nab1/2, YY1, COUP-TFII/NR2F2, YAP/TAZ-TEAD1, c-Jun, Sox2, Zeb2, and Etv1/Er81. These factors can regulate the expression of essential target genes such as Mpz and Mbp in SC myelination and repair. Genetic mutations or dysregulation within this network can lead to peripheral neuropathies such as Charcot-Marie-Tooth disease. However, the transcriptional regulatory network of differentiation, myelination, and remyelination of SCs has not been fully understood yet. Thus, this review briefly introduces processes of differentiation, myelination, and remyelination of SCs and explores the role and molecular mechanisms of each transcription factor and coregulator in differentiation and myelination of SCs and their remyelination following nerve injury. Clinical implications for peripheral neuropathies associated with specific gene mutations and variations of transcription factors and coregulators affecting SC biology are also discussed.