Mutual Antagonism Between Sox10 and NFIA Regulates Diversification of Glial Lineages and Glioma Sub-Types

Lineage progression and diversification is regulated by the coordinated action of unique sets of transcription factors. Oligodendrocytes (OL) and astrocytes (AS) comprise the glial sub-lineages in the central nervous system (CNS) and how their associated regulatory factors orchestrate lineage diversification during development and disease remains an open question. Sox10 and NFIA are key transcriptional regulators of gliogenesis associated with OL and AS. We found that NFIA inhibits Sox10 induction of OL differentiation through direct association and antagonism of its function. Conversely, we found that Sox10 antagonizes NFIA function and suppresses AS differentiation. Using this developmental paradigm as a model for glioma, we found that this relationship similarly regulates the generation of glioma sub-types. These studies describe the antagonistic relationship between Sox10/NFIA that regulates the balance of OL and AS fate during development and demonstrate for the first time that the transcriptional processes governing glial sub-lineage diversification oversee the generation of glioma sub-types.