Genetic networks controlling the development of midbrain dopaminergic neurons

J Physiol. 2006 Sep 1;575(Pt 2):403-10. doi: 10.1113/jphysiol.2006.113464. Epub 2006 Jul 6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Dopamine / metabolism*
  • Gene Expression Regulation, Developmental / genetics*
  • Gene Expression Regulation, Developmental / physiology
  • Hedgehog Proteins
  • Mesencephalon / cytology*
  • Mesencephalon / embryology
  • Mesencephalon / physiology
  • Mice
  • Neurons / cytology*
  • Neurons / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Wnt1 Protein / genetics
  • Wnt1 Protein / metabolism

Substances

  • Hedgehog Proteins
  • SHH protein, human
  • Trans-Activators
  • Transcription Factors
  • Wnt1 Protein
  • Dopamine