Genetic networks controlling the development of midbrain dopaminergic neurons.
Recent data have substantially advanced our understanding of midbrain dopaminergic neuron development. Firstly, a Wnt1-regulated genetic network, including Otx2 and Nkx2-2, and a Shh-controlled genetic cascade, including Lmx1a, Msx1 and Nkx6-1, have been unravelled, 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 (Wnt1 and Lmx1a/Msx1) 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 brain 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 midbrain dopaminergic neuron development in this review.
Prakash
Nilima
N
GSF-National Research Center for Environment and Health, Technical University Munich, Institute of Developmental Genetics, Ingolstaedter Landstr. 1, D-85764 Munich/Neuherberg, Germany.
Wurst
Wolfgang
W
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D004298:Dopamine / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics* / Q000502:physiology; D053823:Hedgehog Proteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D008636:Mesencephalon / Q000166:cytology* / Q000196:embryology / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D009687:Nuclear Proteins; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism
D053823:Hedgehog Proteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; C000715631:NKX2-2 protein, human; C000715627:Nkx2-2 protein, mouse; D009687:Nuclear Proteins; C509239:SHH protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D051155:Wnt1 Protein; D004298:Dopamine