Strategies to unravel molecular codes essential for the development of meso-diencephalic dopaminergic neurons

Understanding the development of neuronal systems has become an important asset in the attempt to solve complex questions about neuropathology as found in Parkinson's disease, schizophrenia and other complex neuronal diseases. The development of anatomical and functional divergent structures in the brain is achieved by a combination of early anatomical patterning and highly coordinated neuronal migration and differentiation events. Fundamental to the existence of divergent structures in the brain is the early region-specific molecular programming. Neuronal progenitors located along the neural tube can still adapt many different identities. Their exact position in the developing brain, however, determines early molecular specification by region-specific signalling molecules. These signals determine time and region-specific expression of early regulatory genes, leading to neuronal differentiation. Here, we focus on a well-described neuronal group, the meso-diencephalic dopaminergic neurons, of which heterogeneity based on anatomical position could account for the difference in vulnerability of specific subgroups as observed in Parkinson's disease. The knowledge of their molecular coding helps us to understand how the meso-diencephalic dopaminergic system is built and could provide clues that unravel mechanisms associated with the neuropathology in complex diseases such as Parkinson's disease.