title: Genome wide expression profiling of the mesodiencephalic region identifies novel factors involved in early and late dopaminergic development.
abstract: Meso-diencephalic dopaminergic (mdDA) neurons are critical for motor control and cognitive functioning and their loss or dysfunction is associated with disorders such as Parkinson's disease (PD), schizophrenia and addiction. However, relatively little is known about the molecular mechanisms underlying mdDA neuron development and maintenance. Here, we determined the spatiotemporal map of genes involved in the development of mdDA neurons to gain further insight into their molecular programming. Genome-wide gene expression profiles of the developing ventral mesencephalon (VM) were compared at different developmental stages leading to the identification of novel regulatory roles of neuronal signaling through nicotinic acthylcholine receptors (Chrna6 and Chrnb3 subunits) and the identification of novel transcription factors (Oc2 and 3) involved in the generation of the mdDA neuronal field. We show here that Pitx3, in cooperation with Nurr1, is the critical component in the activation of the Chrna6 and Chrnb3 subunits in mdDA neurons. Furthermore, we provide evidence of two divergent regulatory pathways resulting in the expression of Chrna6 and Chrnb3 respectively.
authors.affiliation: Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht ,  3584 CG Utrecht ,  The Netherlands.
authors.forename: Koushik
authors.initials: K
authors.lastname: Chakrabarty
authors.forename: Lars
authors.initials: L
authors.lastname: Von Oerthel
authors.forename: Anita
authors.initials: A
authors.lastname: Hellemons
authors.forename: Frédéric
authors.initials: F
authors.lastname: Clotman
authors.forename: Agnès
authors.initials: A
authors.lastname: Espana
authors.forename: Marian
authors.initials: M
authors.lastname: Groot Koerkamp
authors.forename: Frank C P
authors.initials: FC
authors.lastname: Holstege
authors.forename: R Jeroen
authors.initials: RJ
authors.lastname: Pasterkamp
authors.forename: Marten P
authors.initials: MP
authors.lastname: Smidt