There are seventeen cell groups (A1–A17) of catecholamine neurons (dopamine, norepinephrine and epinephrine) within the mammalian brain ranging from medulla to hypothalamus. Only three of them A8 (retrorubral area), A9 (substantia nigra) and A10 (ventral tegmental area) are within mesencephalon. Given their involvement in Parkinson’s disease, a common neurodegenerative disorder, much attention has been devoted to the developmental mechanisms of their generation. Several specific markers, signaling pathways and critical transcription factors have been described that can serve as a roadmap to recreate this particular lineage in reprogramming efforts. Unfortunately, the reported iDaN cells generated so far lack expression of authentic midbrain markers even with induction of six transcription factors characteristic of the dopaminergic lineage [32]. Furthermore, dopaminergic neurons in the midbrain can be further divided into dorsal and ventral tiers [54]. Dopaminergic neurons in the dorsal tier are calbindin positive and express low level of DAT while those in the ventral tier are calbindin negative, mostly GIRK2 positive and express high level of DAT [54]. Dorsal tier dopaminergic neurons are preferentially lost in aging while in Parkinson’s disease degeneration of
