Embryonic stem (ES) cells proliferate extensively, and preliminary data show that animal ES cells can be manipulated to generate highly enriched populations of dopamine neurons that express genes characteristic of midbrain dopamine cells and significantly alleviate behavioral deficits in an animal model of Parkinson's disease. This result encourages further development of the clinical potential of human ES cells. This proposal is to support collaboration between groups at the National Institutes of Health (NIH) and at Rush-Presbyterian Medical Center. The NIH group has experience differentiating ES cells to neuronal and other fates. The Rush group is known for work using primate models to develop new gene therapy approaches to Parkinson's disease. The combination of skills in the two groups will promote rapid assessment of the potential of human ES cells. The proposed experiments will first establish conditions that permit efficient differentiation of human and animal ES cells into dopamine synthesizing neurons. The survival and function of these neurons will then be tested in animal models of Parkinson's disease.