TGF beta superfamily
BMP family
Midbrain dopaminergic neurons
Development
Neurogenesis
GROWTH-FACTOR-BETA
BONE MORPHOGENETIC PROTEINS
NEUROTROPHIC FACTOR GDNF
GROWTH/DIFFERENTIATION FACTOR 5
MICE LACKING GDNF
TYROSINE-HYDROXYLASE EXPRESSION
NERVOUS-SYSTEM DEVELOPMENT
FACTOR IMPROVES SURVIVAL
NEURAL CREST INDUCTION
EMBRYONIC RAT MIDBRAIN
The adult midbrain contains 75 % of all dopaminergic neurons in the CNS. Within the midbrain, these neurons are divided into three anatomically and functionally distinct clusters termed A8, A9 and A10. The A9 group plays a functionally non-redundant role in the control of voluntary movement, which is highlighted by the motor syndrome that results from their progressive degeneration in the neurodegenerative disorder, Parkinson's disease. Despite 50 years of investigation, treatment for Parkinson's disease remains symptomatic, but an intensive research effort has proposed delivering neurotrophic factors to the brain to protect the remaining dopaminergic neurons, or using these neurotrophic factors to differentiate dopaminergic neurons from stem cell sources for cell transplantation. Most neurotrophic factors studied in this context have been members of the transforming growth factor beta (TGF beta) superfamily. In recent years, an intensive research effort has focused on understanding the function of these proteins in midbrain dopaminergic neuron development and their role in the molecular architecture that regulates the development of this brain region, with the goal of applying this knowledge to develop novel therapies for Parkinson's disease. In this review, the current evidence showing that TGF beta superfamily members play critical roles in the regulation of midbrain dopaminergic neuron induction, differentiation, target innervation and survival during embryonic and postnatal development is analysed, and the implications of these findings are discussed.