Role of NCOR1 and NCOR2 transcriptional corepressors in myelin development and remyelination

The transcriptional corepressors NCOR1 and NCOR2 are part of a multiprotein complex that downregulates Jun and triggers the transcription of myelin genes in cultured Schwann cells (SC) (Gomis-Coloma et al., 2018). Both corepressors are also expressed in oligodendrocyte lineage cells, both oligodendrocytes (OL), and in OL precursor cells (OPCs), suggesting that they might contribute to their development and function (Castelo-Branco et al., 2014). Using genetically modified mice we have previously shown that they are dispensable for myelin development in the peripheral nervous system (PNS). In this study we explore their contribution to myelin development and maintenance in the central nervous system (CNS) and their relevance in the remyelination of peripheral nerves after injury. To this aim, we generated conditional double knock-out (dKO) mice in both SC and OL lineage cells (using Sox10-cre and Plp1-creERT2 lines) and explored the distribution of mature OLs in the CNS during development and adulthood, as well as the expression of associated myelin genes. To evaluate regeneration in the PNS, we used the model of nerve transection. We could not find any difference between dKO and control mice. Given the biological relevance of these corepressors, it is plausible that the absence of these genes may be compensated by other redundant genes. However, further studies are necessary to demonstrate this hypothesis.