Distribution, identity and fate of Fgf18-expressing cells in the adult mouse Subventricular zone

In the adult mammalian brain, neurogenesis occurs in specific anatomic regions such as the ventricular-subventricular zone (V-SVZ) and the dentate gyrus of the hippocampus. In the V-SVZ, NSC activation and differentiation is responsible for the generation of inhibitory interneurons in the olfactory bulbs (OBs) that contribute to odour discrimination and related behaviours in mice. Fibroblast Growth Factor (FGF) signalling through their receptors (FGFRs) influence the neurogenic activity of the adult V-SVZ. However, the cohort of FGF members participating in this process has yet to be firmly established. This study investigates the expression of the FGF18-expressing cells in the V-SVZ and follows their fate to determine their involvement in the V-SVZ neurogenic activity. In order to do so, adult FGF18-CreERT2::Rosa26-tdTomato mice were pulsed with tamoxifen for two consecutive days and their brains harvested after either 2 or 12 days later to enable lineage tracing analyses. These findings reveal that, in short chase mice, FGF18-expressing cells were restricted to the dorsal and medial walls of the ventricles whilst in the long chase mice, Tomato+ cells were additionally found in the Rostral Migratory Stream (RMS) and OBs where they resembled migrating neuroblasts and maturating neurons, respectively. In the VSVZ, subsets of FGF18-expressing cells co-expressed the stem cell markers GFAP and Sox2, suggesting that they may be NSCs/progenitor cells and regulate neurogenesis. Eventually, they might have a role in barrier function at the ependymal layer of the niche. Analyses of early postnatal mice revealed an age-dependent expression and activity of the FGF18-expressing cells in the V-SVZ niche and daughter cells. Together, this study points to a dynamic participation of FGF18 in the neurogenic activity and homeostasis preservation of the adult mouse V-SVZ, opening new scenarios on the regulatory role of FGF signalling in this region