Intraventricular injection of FGF‐2 promotes generation of oligodendrocyte‐lineage cells in the postnatal and adult forebrain

Abstract

FGF2 is considered a key factor in the generation of oligodendrocytes (OLs) derived from neural stem cells (NSCs) located within the subventricular zone (SVZ). Here, we have examined FGF2 signaling in the forebrain of postnatal and adult mice. Using qPCR of microdissected microdomains of the dorsal SVZ (dSVZ) and lateral SVZ (lSVZ), and prominin1-sorted NSCs purified from these microdomains, we show that transcripts for FGF receptor 1 (FGFR1) and FGFR2 are enriched in the dSVZ, from which OLs are largely derived, whereas FGFR3 are significantly enriched within prominen1-sorted NSC of the lSVZ, which mainly generate olfactory interneurons. We show that direct administration of FGF2 into the lateral ventricle increased the generation of oligodendrocyte progenitors (OPCs) throughout the SVZ, both within the dSVZ and ectopically in the lSVZ and ependymal wall of the SVZ. Furthermore, FGF2 stimulated proliferation of neural progenitors (NPs) and their differentiation into OPCs. The results indicate that FGF2 increased specification of OPCs, inducing NPs to follow an oligodendrocyte developmental pathway. Notably, FGF2 did not block OPC differentiation and increased the number of oligodendrocytes in the periventricular white matter (PVWM) and cortex. However, FGF2 markedly disrupted myelination in the PVWM. A key finding was that FGF2 had equivalent actions on the generation of OPCs and myelin disruption in postnatal and adult mice. This study demonstrates a central role for FGF2 in promoting oligodendrocyte generation in the developing and adult brain.