Another clinically relevant neuronal subtype that has been under intense investigation is the group of midbrain dopaminergic (DA) neurons, which are preferentially affected in Parkinson’s disease. Recently, two important proof-of-principle studies described the generation of iN cells expressing tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis (Caiazzo et al., 2011; Pfisterer et al., 2011). Pfisterer et al. showed that Lmx1a and Foxa2, when used in conjunction with the BAM pool, are capable of generating iN cells expressing TH, Aromatic L-amino acid decarboxylase (AADC), another crucial enzyme in catecholamine biosynthesis, and importantly, Nurr1, a marker of midbrain identity. However, the cells did not express other midbrain markers and were not able to release dopamine into the media. Another report by Caiazzo et al. demonstrated the generation of mouse iN cells with dopaminergic features by expression of the transcription factors Ascl1, Nurr1 and Lmx1a. The efficiency of induction of TH-positive cells was reported to be 18% relying on a TH-EGFP transgenic reporter line. The TH-positive cells co-expressed vesicular monoamine transporter 2 (VMAT2), dopamine transporter (DAT), aldehyde dehydrogenase 1a1 (ALDH1A1), and calbindin.
