Making connections: the development of mesencephalic dopaminergic neurons

The disorders of two adjacent sets of mesencephalic dopaminergic neurons (MDNs) are associated with two significant health problems: Parkinson's disease and drug addiction. Because of this, a great deal of research has focused on understanding the growth, development and maintenance of MDNs. Many transcription factors and signaling pathways are known to be required for normal MDNs formation, but a unified model of MDN development is still unclear. The long-term goal is to design therapeutic strategies to: (i) nurture and/or heal endogenous MDNs, (ii) replace the affected tissue with exogenous MDNs from in vitro cultivated stem cells and (iii) restore normal connectivity. Recent developmental biology studies show great promise in understanding how MDNs develop both in vivo and in vitro. This information has great therapeutic value and may provide insight into how environmental and genetic factors increase vulnerability to addiction. (C) 2003 Elsevier B.V All rights reserved.