Myelin is essential for the rapidity of saltatory nerve conduction, and also provides trophic support for axons to prevent axonal degeneration. Two critical determinants of myeiination are SOXIO and EGR2/ KROX20. SOXIO is required for specification ofSchwann cells from neural crest, and is required at every stage of Schwann cell development. Egr2/ Krox20 expression is activated by axonal signals in myelinating Schwann cells, and is required for cell cycle arrest and myelin formation. To elucidate the integrated function of these two transcription factors during peripheral nerve myeiination, we performed in vivo ChlP-Seq analysis of myelinating peripheral nerve. Integration of these binding data with loss-of-function array data identified a range ofgenes regulated by these factors. In addition, although SOXIO itself regulates Egr2/Krox20 expression, leading to coordinate activation of several major myelin genes by the two factors, there is a large subset of genes that are activated independent ofEGR2. Finally, the results identify a set of SOX10-dependent genes that are expressed in early Schwann cell development, but become subsequently repressed by EGR2/KR0X20.
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