Brg1-Dependent Chromatin Remodelling Is Not Essentially Required during Oligodendroglial Differentiation

Abstract

Myelinating Schwann cells in the vertebrate peripheral nervous system rely on Brg1 (Smarca4) for terminal differentiation. Brg1 serves as central ATP-hydrolyzing subunit of the chromatin remodelling BAF complexes and is recruited during myelination as part of these complexes by the transcription factor Sox10 in Schwann cells. Here, we analyzed the role of Brg1 during development of myelinating oligodendrocytes in the CNS of the mouse. Following Brg1 deletion in oligodendrocyte precursors, these cells showed normal survival, proliferation, and migration. A mild but significant reduction in the number of oligodendrocytes with myelin gene expression in the absence of Brg1 points to a contribution to oligodendroglial differentiation but also shows that the role of Brg1 is much less prominent than during Schwann cell differentiation. Additionally, we failed to obtain evidence for a genetic interaction between Brg1 and Sox10 comparable with the one in Schwann cells. This argues that similarities exist between the regulatory networks and mechanisms in both types of myelinating glia but that the exact mode of action and the relevance of functional interactions differ, pointing to a surprising degree of variability in the control of myelination.