Recent data have substantially advanced our understanding of midbrain dopaminergic neuron development. Firstly, a Wntl-regulated genetic network, including Otx2 and Nkx2-2, and a Shh-controlled genetic cascade, including Lmxl a, Msxl and Nkx6-1, have been unr avelled, acting in parallel or sequentially to establish a territory competent for midbrain dopaminergic precursor production at relatively early stages of neural development. Secondly, the same factors (Wntl and Lmxla/Msxl) appear to regulate midbrain dopaminergic and/or neuronal fate specification in the postmitotic progeny of these precursors by controlling the expression of midbrain dopaminergic-specific and/or general proneural factors at later stages of neural development. For the first time, early inductive events have thus been linked to later differentiation processes in midbrain dopaminergic neuron development. Given the pivotal importance of this neuronal population for normal function of the human br ain and its involvement in severe neurological and psychiatric disorders such as Parkinson's Disease, these advances open new prospects for potential stem cell-based therapies. We will summarize these new findings in the overall context of midbr ain dopaminergic neuron development in this review.
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