Pitx3 is required for development of substantia nigra dopaminergic neurons

Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4245-50. doi: 10.1073/pnas.0230529100. Epub 2003 Mar 24.

Abstract

Dopaminergic (DA) neurons of substantia nigra in the midbrain control voluntary movement, and their degeneration is the cause of Parkinson's disease. The complete set of genes required to specifically determine the development of midbrain DA subgroups is not known yet. We report here that mice lacking the bicoid-related homeoprotein Pitx3 fail to develop DA neurons of the substantia nigra. Other mesencephalic DA neurons of the ventral tegmental area and retrorubral field are unaltered in their dopamine expression and histological organization. These data suggest that Pitx3-dependent gene expression is specifically required for the differentiation of DA progenitors within the mesencephalic DA system.

Publication types

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

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Animals, Newborn
  • Aphakia / genetics
  • Aphakia / physiopathology
  • Corpus Striatum / metabolism
  • Dopamine / physiology*
  • Gene Expression Regulation, Developmental / physiology*
  • Heterozygote
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / physiology
  • Immunohistochemistry
  • Mesencephalon / growth & development
  • Mesencephalon / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / physiology*
  • Substantia Nigra / growth & development*
  • Transcription Factors / deficiency
  • Transcription Factors / genetics*
  • Transcription Factors / physiology
  • Tyrosine 3-Monooxygenase / analysis

Substances

  • Homeodomain Proteins
  • Transcription Factors
  • homeobox protein PITX3
  • 3,4-Dihydroxyphenylacetic Acid
  • Tyrosine 3-Monooxygenase
  • Dopamine