GABAergic and glutamatergic identities of developing midbrain Pitx2 neurons

Dev Dyn. 2011 Feb;240(2):333-46. doi: 10.1002/dvdy.22532. Epub 2011 Jan 11.


Pitx2, a paired-like homeodomain transcription factor, is expressed in post-mitotic neurons within highly restricted domains of the embryonic mouse brain. Previous reports identified critical roles for PITX2 in histogenesis of the hypothalamus and midbrain, but the cellular identities of PITX2-positive neurons in these regions were not fully explored. This study characterizes Pitx2 expression with respect to midbrain transcription factor and neurotransmitter phenotypes in mid-to-late mouse gestation. In the dorsal midbrain, we identified Pitx2-positive neurons in the stratum griseum intermedium (SGI) as GABAergic and observed a requirement for PITX2 in GABAergic differentiation. We also identified two Pitx2-positive neuronal populations in the ventral midbrain, the red nucleus, and a ventromedial population, both of which contain glutamatergic precursors. Our data suggest that PITX2 is present in regionally restricted subpopulations of midbrain neurons and may have unique functions that promote GABAergic and glutamatergic differentiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Glutamic Acid / metabolism*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Mesencephalon / cytology*
  • Mesencephalon / embryology*
  • Mesencephalon / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neurons / cytology
  • Neurons / physiology*
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • gamma-Aminobutyric Acid / metabolism*


  • Homeodomain Proteins
  • Transcription Factors
  • homeobox protein PITX2
  • Glutamic Acid
  • gamma-Aminobutyric Acid