Abstract
Oligodendrocytes are responsible for axon myelination in the brain and spinal cord. Generation of oligodendrocytes entails highly regulated multistage neurodevelopmental events, including proliferation, differentiation and maturation. The chromatin remodeling BAF (mSWI/SNF) complex is a notable regulator of neural development. In our previous studies, we determined the indispensability of the BAF complex scaffolding subunits BAF155 and BAF170 for neurogenesis, whereas their role in gliogenesis is unknown. Here, we show that the expression of BAF155 and BAF170 is essential for the genesis of oligodendrocytes during brain development. We report that the ablation of BAF155 and BAF170 in the dorsal telencephalic (dTel) neural progenitors or in oligodendrocyte-producing progenitors in the ventral telencephalon (vTel) in double-conditional knockout (dcKO) mouse mutants, perturbed the process of oligodendrogenesis. Molecular marker and cell cycle analyses revealed impairment of oligodendrocyte precursor specification and proliferation, as well as overt depletion of oligodendrocytes pool in dcKO mutants. Our findings unveil a central role of BAF155 and BAF170 in oligodendrogenesis, and thus substantiate the involvement of the BAF complex in the production of oligodendrocytes in the forebrain.
Highlights
During mammalian brain development, the telencephalic radial glial cells (RGCs) generate diverse neuronal and non-neuronal cell types; the latter includes astrocytes, and oligodendrocytes (OLs) (Rowitch and Kriegstein, 2010)
We found that the conditional deletion of the ATP-dependent chromatin remodeling BRG1/BRMassociated factor (BAF) complex scaffolding subunits BAF155 and BAF170 in the developing forebrain resulted in improper specification and proliferation of oligodendrocyte precursor cells (OPCs) leading to impairment of oligodendrogenesis
We found in our previous investigations that inactivation of BAF complex by ablation of its scaffolding subunits BAF155 and BAF170 during early or late corticogenesis impairs the cortical progenitor pool, with concomitant disturbance of neurogenesis in the prenatal and early postnatal mouse cortex (Narayanan et al, 2015; Nguyen et al, 2018)
Summary
The telencephalic radial glial cells (RGCs) generate diverse neuronal and non-neuronal cell types; the latter includes astrocytes, and oligodendrocytes (OLs) (Rowitch and Kriegstein, 2010). Generation of mature myelinating OLs is a sequential multistep process commencing with the specification of multipotent RGCs into oligodendrocyte precursor cells (OPCs) (Richardson et al, 2006; Rowitch and Kriegstein, 2010). Further in the oligodendroglial lineage progression, the highly proliferative and migratory OPCs acquire differentiative fate to become immature OLs, which subsequently undergo maturation to become myelinating OLs (Richardson et al, 2006; Rowitch and Kriegstein, 2010). The latest group of newly born OPCs are derived from Emx1-expressing progenitors in the neocortex at birth, and constitute the OPC pool in adulthood (Kessaris et al, 2006; Richardson et al, 2006; Naruse et al, 2017)
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