Mechanisms regulating GABAergic neuron development

Cell Mol Life Sci. 2014 Apr;71(8):1395-415. doi: 10.1007/s00018-013-1501-3. Epub 2013 Nov 7.

Abstract

Neurons using gamma-aminobutyric acid (GABA) as their neurotransmitter are the main inhibitory neurons in the mature central nervous system (CNS) and show great variation in their form and function. GABAergic neurons are produced in all of the main domains of the CNS, where they develop from discrete regions of the neuroepithelium. Here, we review the gene expression and regulatory mechanisms controlling the main steps of GABAergic neuron development: early patterning of the proliferative neuroepithelium, production of postmitotic neural precursors, establishment of their identity and migration. By comparing the molecular regulation of these events across CNS, we broadly identify three regions utilizing distinct molecular toolkits for GABAergic fate determination: telencephalon-anterior diencephalon (DLX2 type), posterior diencephalon-midbrain (GATA2 type) and hindbrain-spinal cord (PTF1A and TAL1 types). Similarities and differences in the molecular regulatory mechanisms reveal the core determinants of a GABAergic neuron as well as provide insights into generation of the vast diversity of these neurons.

Publication types

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

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Body Patterning / physiology
  • Cell Differentiation / physiology*
  • Cell Lineage / physiology
  • Cell Movement / physiology
  • Central Nervous System / cytology
  • Central Nervous System / embryology*
  • GABAergic Neurons / classification
  • GABAergic Neurons / cytology*
  • GABAergic Neurons / physiology*
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Developmental / physiology*
  • Humans
  • Models, Biological*
  • Neurogenesis / physiology*
  • Proto-Oncogene Proteins / metabolism
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Transcription Factors / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Proto-Oncogene Proteins
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Transcription Factors
  • transcription factor PTF1
  • TAL1 protein, human