protein (APP) puncta in endosomes, which was not readily detected in the originating FAD fibroblasts. This phenotype could be rescued by overexpression of wild-type PRESENELIN1. Of note, one of the reprogramming factors used in this study is Olig2, another member of bHLH family. Olig2 is not specific to neurons and can promote both neuronal and oligodendroglial fates depending on the developmental context (Mizuguchi et al., 2001; Novitch et al., 2001; Zhou et al., 2001; Lu et al., 2002; Park et al., 2002; Takebayashi et al., 2002). However, in contrast to Ascl1 and NeuroD1, Olig2 is thought to act as a repressor, and associate with Ngn2 and E47 to antagonize their neurogenic effect (Lee et al., 2005). Future work will need to elucidate the function of these transcription factors during reprogramming. As a number of different transcription factor combinations can induce neuronal cells, there may be several parallel pathways to the neuronal lineage. Alternatively, the different transcription factors may eventually activate the same core program to induce neuronal identity.
