We have in the first funding year successfully generated the mouse strains required for the proposed experiments. In particular, we have generated FMRP mutant mice that also harbor the TauEGFP allele which allows the identification and purification of induced neuronal (iN) cells. We have also successfully established mouse embryonic fibroblast and tail-tip derived fibroblast cultures from these mice. Moreover, we successfully generated iN cells from these mice and characterized them molecularly. They are also being analyzed electrophysiologically in the Chen lab (see her report). Moreover, we have made very good progress in converting also human fibroblasts into iN cells. Systematic screening of additional transcription factors has revealed that the addition of NeuroD1 greatly enhances the efficiency to convert human fibroblasts into iN cells and in this condition we were also able to generate cells that are synaptically competent. However, the efficiencies are still much lower than using mouse cells and we are currently trying to improve these efficiencies.