Development and Engineering of Dopamine Neurons

Theneurotransmitter dopamine has just celebrated its 50thbirthday. The discovery of dopamine as a neuronal entity in the late 1950s and the notion that it serves in neurotransmission has been a milestone in the field of neuroscience research. This milestone marked the beginning of an era that explored the brain as an integrated collection of neuronal systems that one could distinguish on basis of neurotransm- ter identities, and importantly, in which one started to be able to pinpoint the seat of brain disease. The mesodiencephalic dopaminergic (mdDA) system, previously designated as midbraindopaminergic system, has received much attention since its discovery. The initial identification of dopamine as a neurotransmitter in the central nervous system (CNS) and its relevance to psychiatric and neurological disorders have stimulated a plethora of neurochemical, pharmacological and genetic studies into the function of dopamine neurons and theirprojections. In the last decade, studies on gene expression and development have further increased the knowledge of this neuronal population and have unmasked a new level of complexity. The start of the molecular dissection of the mdDA system has been marked by the cloning and characterization ofNurrl and Pitx3. These transcription factors were shown to have a critical function during mdDA development. These initial studies have been followed by the identification of many other proteins, which have a crucial function in the creation of a dopamine neuron permissive region, induction of precursors, induction of terminaldifferent- tion and finally maintenance of the mdDA neuronal pool.

R. Jeroen Pasterkamp is an Assistant Professor at the Rudolf Magnus
Institute of Neuroscience, Department of Neuroscience and Pharmacology, University
Medical Center Utrecht, Utrecht, The Netherlands. The focus of his laboratory is
directed towards understanding the molecular and intracellular signaling events
involved in the formation of neuronal connections with a particular focus on the
developing dopamine system. His research team concentrates on the developing
mouse embryo using an integrated approach involving molecular biology, cell biology,
in vivo functional proteomics, and mouse genetics. He received his PhD from
the Netherlands Institute for Neurosciences (Amsterdam, The Netherlands) and
did his Postdoctoral at the Department of Neuroscience, Johns Hopkins University
School of Medicine, Baltimore, USA.

Marten Smidt is an Associate Professor at the Rudolf Magnus Institute
of Neuroscience, Department of Neuroscience and Pharmacology, University
Medical Center Utrecht, Utrecht, The Netherlands. The focus of his laboratory is
directed towards understanding the developmental processes that underlie neuronal
differentiation and specification. The main focus has been the development of
mesodiencephalic dopamine neurons. The work includes mouse genetics, molecular
genetics and molecular biology. Marten Smidt received his PhD from the University
of Groningen (Groningen, The Netherlands) and did his postdoctoral at Utrecht
University, Department of Medical Pharmacology, Rudolf Magnus Institute of
Neuroscience (Utrecht, The Netherlands).

J. Peter H. Burbach is professor of Molecular Neuroscience at Utrecht
University and head of the Department of Neuroscience and Pharmacology, Rudolf
Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The
Netherlands. His research interests concern the role of transcriptionfactors in development and regulation of peptidergic and dopaminergic neurons, and the molecular
mechanisms of human neurodevelopmental disorders. He received his PhD from
Utrecht University and did postdoctoral work at the Clinical Research Institute of
Montreal, Canada. He obtained professorships in Molecular Biology and Molecular
Neuroendocrinology. Since 2001 he is a Summer scientist at the Marine Biological
Laboratory, Woods Hole, MA, USA.