Effect of depletion of Prrc2b on gene expression during neural development in isloated neural stem cells of C57BL/6J mice.

Oligodendrocytes (OLs), the myelin-producing cell in brain, are necessary for maintaining brain homeostasis and higher nervous activity. Deficiency of OLs development affects the formation and function of myelin sheath and results in neurological diseases. N6-methyladenosine (m6A) is the most abundant modification in mammalian mRNA, but the exact mechanism of m6A in OL specification remains unclear. Here, we identified that Prrc2b is a m6A-reading protein and regulates oligodendrocyte development and myelination. Nestin-Cre-mediated Prrc2b deletion affects neural stem cell proliferation and glia differentiation. Moreover, oligodendroglial-lineage specific deletion of Prrc2b reduced numbers of oligodendrocyte progenitor cells (OPCs) and OLs, causing hypomyelination and impaired motor coordination in mice. Integrated analysis of m6A-seq, RNA-seq and Prrc2b RIP-seq, we found that Sox2 is the critical target of Prrc2b in OL development