"The goal of this project is to determine whether the expression of developmental genes in defined subpopulations of DA neurons contributes to the specification of currently unrecognized midbrain DA neuron subtypes and whether their missexpression may contribute to the loss of DA neurons in the adulthood and to the pathogenesis of PD.Many developmental genes have been found to be implicated in the maintenance of midbrain DA neurons at postnatal and adult stages, as assessed by the loss of DA neurons in transgenic mice heterozygous for: Nurr1, Pitx3, FoxA2, en1. On the other hand, genes involved in the pathogenesis of genetic forms of PD, such as Lrkk2 and PINK1, do not cause cell death. In this project we hypothesize that a disregulation of the expression of developmental genes may play a previously unrecognized role in PD.We propose to identify subtypes of midbrain DA neurons at a molecular and functional level in: (i) the developing rodent and human ventral midbrain (VM), (ii) human neural and embryonic stem cell preparations differentiated into midbrain DA neurons, and (iii) DA neurons derived from induced pluripotent stem (iPS) cells generated from control and PD patients."