The transcriptional regulation of the development of midbrain dopaminergic neurons

The degeneration of dopaminergic neurons in the substantia nigra of the midbrain is one of the main features of the Parkinson’s disease, responsible for the motor symptoms. The development of these neurons is under the tight control of a set of transcription factors. These factors contribute to the development of several neuronal properties of the dopaminergic neurons, including their morphology, their neurotransmitter phenotype as well as their inherent vulnerability to degeneration. Several environmental and genetic factors have been identified as the contributing causes of the disease. The developmental transcription factors may not only regulate the expression of the genetic factors, they may also contribute to the uptake of, susceptibility toward and response to the toxic agents known to specifically target the dopaminergic neurons. In this work, I will review role of the midbrain developmental transcription factors during the early, intermediate and late development of the dopaminergic neurons, i.e. their neurogenesis, differentiation and maturation. An important area of investigation has been the role of developmental factors beyond these developmental stages. I will discuss the function of each transcription factor in the survival and maintenance of postmitotic neurons postnatally and throughout the life of a species. I will also discuss the direct and indirect connection between these factors and pathogenesis of Parkinson’s disease. Understanding the cellular signaling pathways involved in the development, survival and maintenance of the midbrain dopaminergic neurons may lead to the development of novel therapeutic approaches for Parkinson’s disease.