Fig. 2

Effect of RAS signaling components on neural stem cell differentiation. Neural stem cells are able to generate progeny cells that terminally differentiate into neurons, oligodendrocytes, and astrocytes. a NF1 inactivation led to decreased neurogenesis in neonatal and adult mouse brains [85]. PTPN11 positively regulates neurogenesis at the expense of gliogenesis [96]. b NF1 negatively regulates gliogenesis, thus NF1 inactivation increases the number of glial progenitor cells and gliogenesis [78, 79, 85, 89, 159, 160]. PTPN11 suppresses gliogenesis by directly interacting with the JAK-STAT pathway, which promotes gliogenesis [92, 96]. c Hyperactivation of RAF1 induces the increase of glial lineage populations, including oligodendrocyte progenitor cells and astrocytes [107]. MEK is required for gliogenesis, and the hyperfunction of MEK1 leads to increase in glial populations [108, 109]. d BRAF and RAF1 positively regulate neuronal differentiation, and the disruption of BRAF or RAF1 impairs the ability of progenitor cells to differentiate into mature neurons in mouse brain [102, 105]. In consistent, iPSC containing hyperactivated BRAF mutant showed early maturation of neurons [190]. e Oligodendroglial lineage potential is restricted by NF1 in the adult hippocampus, and inactivation of NF1 allows the adult hippocampus to generate oligodendrocytes [85]. f BRAF is required for oligodendrocyte maturation and myelination during postnatal development [103]. g Hyperactivated HRAS leads to an acceleration of astroglial maturation [206, 211]. Blue and red arrows indicate positive and negative regulation, respectively.