Distinct developmental origins and regulatory mechanisms for GABAergic neurons associated with dopaminergic nuclei in the ventral mesodiencephalic region

Development. 2012 Jul;139(13):2360-70. doi: 10.1242/dev.076380. Epub 2012 May 23.

Abstract

GABAergic neurons in the ventral mesodiencephalic region are highly important for the function of dopaminergic pathways that regulate multiple aspects of behavior. However, development of these neurons is poorly understood. We recently showed that molecular regulation of differentiation of the GABAergic neurons associated with the dopaminergic nuclei in the ventral midbrain (VTA and SNpr) is distinct from the rest of midbrain, but the reason for this difference remained elusive. Here, we have analyzed the developmental origin of the VTA and SNpr GABAergic neurons by genetic fate mapping. We demonstrate that the majority of these GABAergic neurons originate outside the midbrain, from rhombomere 1, and move into the ventral midbrain only as postmitotic neuronal precursors. We further show that Gata2, Gata3 and Tal1 define a subpopulation of GABAergic precursors in ventral rhombomere 1. A failure in GABAergic neuron differentiation in this region correlates with loss of VTA and SNpr GABAergic neurons in Tal1 mutant mice. In contrast to midbrain, GABAergic neurons of the anterior SNpr in the diencephalon are not derived from the rhombomere 1. These results suggest unique migratory pathways for the precursors of important GABAergic neuron subpopulations, and provide the basis for understanding diversity within midbrain GABAergic neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / analysis
  • Cell Lineage
  • Cell Movement
  • Dopaminergic Neurons / physiology*
  • Embryonic Development
  • Female
  • GABAergic Neurons / physiology*
  • GATA2 Transcription Factor / analysis
  • GATA3 Transcription Factor / analysis
  • Mice
  • Proto-Oncogene Proteins / analysis
  • Substantia Nigra / cytology
  • Substantia Nigra / growth & development*
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Ventral Tegmental Area / cytology
  • Ventral Tegmental Area / growth & development*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • GATA2 Transcription Factor
  • GATA3 Transcription Factor
  • Gata2 protein, mouse
  • Gata3 protein, mouse
  • Proto-Oncogene Proteins
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Tal1 protein, mouse