A postnatal progenitor cell population in the mouse cerebral cortex negatively regulated by Fgf10

There is growing evidence that neurogenesis is widespread within the postnatal/adult brain, in areas overlapping with expression of Fibroblast growth factor 10 (Fgf10) which is postulated as consistent with neural progenitor cell identity. To test this hypothesis in the postnatal cortex, 4-day old Fgf10CreERT2::Rosa26-tdTomato double- transgenic pups were tamoxifen-treated to activate tdTomato expression (Tom), and brains analysed at multiple stages thereafter. At each postnatal age Tom+ cells were sparsely scattered throughout the cortex forming isolated ‘clones’. The Tom+ cells were scrutinised for expression of markers of neurons, intermediate progenitors, and proliferating cells, and scored for clone size, laminar and rostro-caudal distribution. To understand the role of Fgf10, parallel experiments were performed after its conditional deletion in Fgf10CreERT2/floxed::Rosa-tdTomato triple-transgenic mice. The ‘clone’ size, distribution and identity of Fgf10-deficient Tom+ cells was then compared to the Fgf10CreERT2/+ condition. In both models, Tom+ cells amplified and differentiated into both pyramidal and non- pyramidal neurons, and rare glial cells. Moreover, Tom+ cells were distributed within all cortical laminae and across the rostro-caudal axis, with a majority populating the deep cortical layers and caudal regions. Strikingly, Fgf10-deficiency enhanced the amplification of Tom+ cells resulting in more two-cell and greater Tom+ clones, suggesting that loss of Fgf10 induces at least one extra cell division. This was corroborated by detection of PCNA+ Tom+ cells. Surprisingly, no FGF10+ cells were observed within the embryonic cortical germinal zones but were evident within the meninges after birth. Finally, FGF10’s cognate receptors – Fgfr1-IIIb and Fgfr2-IIIb isoforms were not expressed in the postnatal cortex, indicating a non-canonical mode of FGF10 action, possibly involving its recently-identified intracellular function. This indicates that postnatal cortical FGF10+ cells exhibit characteristics of quiescent neural stem/progenitors, and that FGF10 normally represses neurogenesis. The novel cell populations identified here may be beneficial for approaches in prompting brain repair after injury or ageing