Transcriptional control of GABAergic neuronal subtype identity in the thalamus

Neural Dev. 2014 Jun 15:9:14. doi: 10.1186/1749-8104-9-14.

Abstract

Background: The thalamus is often defined as the 'gateway to consciousness', a feature that is supported by the specific connectivity and electrophysiological properties of its neurons. Inhibitory GABAergic neurons are required for the dynamic gating of information passing through the thalamus. The high degree of heterogeneity among thalamic GABA neurons suggests that, during embryonic development, alternative differentiation programmes exist to guide the acquisition of inhibitory neuron subtype identity.

Results: Taking advantage of the accessibility of the developing chick embryo, we have used in ovo manipulations of gene expression to test the role of candidate transcription factors in controlling GABAergic neuronal subtype identity in the developing thalamus.

Conclusions: In this study, we describe two alternative differentiation programmes for GABAergic neurogenesis in the thalamus and identify Helt and Dlx2 as key transcription factors that are sufficient to direct neuronal progenitors along a specific differentiation pathway at the expense of alternative lineage choices. Furthermore, we identify Calb2, a gene encoding for the GABA subtype marker calretinin as a target of the transcription factor Sox14. This work is a step forward in our understanding of how GABA neuron diversity in the thalamus is achieved during development and will help future investigation of the molecular mechanisms that lead up to the acquisition of different synaptic targets and electrophysiological features of mature thalamic inhibitory neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Chick Embryo
  • GABAergic Neurons / classification
  • GABAergic Neurons / metabolism*
  • Homeodomain Proteins / metabolism
  • Mice
  • Neurogenesis / genetics*
  • Repressor Proteins / metabolism
  • SOXB2 Transcription Factors / metabolism
  • Thalamus / embryology*
  • Transcription Factors / metabolism
  • Transcription, Genetic

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Distal-less homeobox proteins
  • Helt protein, mouse
  • Homeodomain Proteins
  • Repressor Proteins
  • SOXB2 Transcription Factors
  • Sox14 protein, mouse
  • Transcription Factors