Specifically blocking nFGFR1 signaling with a nuclear dominant negative FGFR1(SP-/NLS)(TK-) in hESCs or in human or mouse NPCs blocked their neuronal differentiation and development. On the other hand, transfection of a nuclear constitutively active FGFR1(SP-/NLS) was sufficient to induce neuron development, sometimes producing unusually large neurons28,52. Together these loss and gain of function experiments demonstrated the importance of nFGFR1 homeostasis in neuronal development. Similar observations, albeit limited by the efficiency of in vivo transfection, were made upon nFGFR1 and nuclear FGF2 transfections of mouse brain stem cells53,54.
