C O M M E N TA R Y Open Access

Parkinson’s disease are caused by DA neuron degeneration. Several other disorders, including schizophrenia and addiction, are associated with abnormal dopamine neurotransmission. Thus, the prospect of engineering DA neurons from stem cells has attracted considerable interest as it could provide opportunities for more advanced in vitro cellular models, allowing refined methods for drug development, and for cell replacement in patients with Parkinson’s disease. However, stem-cell engineering requires detailed knowledge of how DA neurons are generated in normal embryogenesis, which in part explains a strong focus in previous studies on ventral midbrain development [3]. Although key signaling events and transcription factors important for the development of all DA neurons have been identified, much remains to be uncovered. Notably, the midbrain DA neurons can be subdivided into several anatomically and functionally distinct subgroups, but little is known about how these different types are specified. The rostrally, laterally located DA neurons of the substantia nigra pars compacta (SNc) are involved in motor control, and are the cells that mainly undergo degeneration in Parkinson’s disease. Neurons of the ventral tegmental area (VTA) and retrorubal field are located at a caudal, medial position in the ventral midbrain and are part of the mesocorticolimbic system. Abnormal functioning of the limbic system is associated with psychiatric disorders, including addiction and schizophrenia. The different types of DA neurons resemble each other but their axon targets are distinct. Neurons of the SNc innervate the dorsal striatum while VTA neurons mainly innervate the more ventrally located nucleus accumbens and the prefrontal cortex. It remains unclear if these distinct DA neuron subtypes are developmentally specified at an early progenitor stage or if events in postmitotic neurons determine their subtype identity. Moreover, although recent studies have defined molecular markers that are uniquely expressed in distinct DA neuron progenitor domains, the lineage relationships between spatially distinct progenitors and different DA