The developmental road of a dopamine neuron: In search of novel factors in mdDA neuronal development

Mesodiencephalic dopaminergic (mdDA) neurons are involved in motivation, reward, and movement systems in the brain. This group of neurons can be subdivided into different subsets of neurons, which becomes specifically clear during Parkinson’s Disease (PD), when neurons of the substantia nigra degenerate, whereas neurons of the VTA remain relatively intact. Why the degeneration during PD mainly affects neurons of the SNc and how these subsets of neurons are specified remains unclear.
In this thesis we have tried to answer the question how neural progenitor cells in the ventricular zone of the midbrain are specified to become mdDA neurons and how these neurons obtain a subset-specific identity. By means of gene expression analysis we have identified 6 factors that could have a role in the development of these neurons. We have shown that 3 previously unknown factors have a function in early specification of neural progenitor cells and/or late differentiation into the different subsets. Furthermore, we show that one of these factors also has a function in cortical development. Besides these experiments we have developed a technique to electroporate developing mdDA neurons and thereby manipulating gene expression.
The research performed in this thesis provides novel insights in the factors that are important in the development of mdDA neurons and the different subsets. This knowledge can be used in optimizing protocols to culture the correct set of mdDA neurons to use for cell-transplantation therapies in patients with PD.