Understanding how the different cells of the brain are generated during embryonic development is one of the fundamental questions in biology. Recent studies have elucidated several key mechanisms explaining how different neuronal cell types are generated. However, surprisingly little is known about the process that underlies the generation of the dopamine cells that degenerate in Parkinson’s disease. Elucidating the molecular program that control the generation of dopamine cells should facilitate strategies to generate dopamine neurons from stem cells and may also have relevance for understanding the pathology of dopamine neurons in Parkinson’s patients. In preliminary experiments, we have identified several novel factors implicated in dopamine cell generation. In this project, we aim to characterize the functional role of these factors in developing dopamine cells, and further examine the possible use of these factors to effectively produce dopamine neurons from stem cells.
Drs. Ericson and Perlmann identified Lmx1a as key determinant in dopaminergic (DA) neuron development and demonstrated the ability to promote robust human embryonic stem cell-to-DA neuron differentiation. These results led to additional support from MJFF.