The early fetal development of human neocortical GABAergic interneurons

Cereb Cortex. 2015 Mar;25(3):631-45. doi: 10.1093/cercor/bht254. Epub 2013 Sep 18.

Abstract

GABAergic interneurons are crucial to controlling the excitability and responsiveness of cortical circuitry. Their developmental origin may differ between rodents and human. We have demonstrated the expression of 12 GABAergic interneuron-associated genes in samples from human neocortex by quantitative rtPCR from 8 to 12 postconceptional weeks (PCW) and shown a significant anterior to posterior expression gradient, confirmed by in situ hybridization or immunohistochemistry for GAD1 and 2, DLX1, 2, and 5, ASCL1, OLIG2, and CALB2. Following cortical plate (CP) formation from 8 to 9 PCW, a proportion of cells were strongly stained for all these markers in the CP and presubplate. ASCL1 and DLX2 maintained high expression in the proliferative zones and showed extensive immunofluorescent double-labeling with the cell division marker Ki-67. CALB2-positive cells increased steadily in the SVZ/VZ from 10 PCW but were not double-labeled with Ki-67. Expression of GABAergic genes was generally higher in the dorsal pallium than in the ganglionic eminences, with lower expression in the intervening ventral pallium. It is widely accepted that the cortical proliferative zones may generate CALB2-positive interneurons from mid-gestation; we now show that the anterior neocortical proliferative layers especially may be a rich source of interneurons in the early neocortex.

Keywords: DLX genes; GABA; GABRB3; cerebral cortex; inhibitory interneurons; neurodevelopmental disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Calbindin 2 / genetics
  • Cell Division
  • GABAergic Neurons / cytology
  • GABAergic Neurons / metabolism*
  • Gene Expression
  • Glutamate Decarboxylase / genetics
  • Homeodomain Proteins / genetics
  • Humans
  • Interneurons / cytology
  • Interneurons / metabolism*
  • Neocortex / embryology*
  • Nerve Tissue Proteins / genetics
  • Oligodendrocyte Transcription Factor 2
  • Real-Time Polymerase Chain Reaction
  • Transcription Factors / genetics

Substances

  • ASCL1 protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • CALB2 protein, human
  • Calbindin 2
  • Distal-less homeobox proteins
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • OLIG2 protein, human
  • Oligodendrocyte Transcription Factor 2
  • Transcription Factors
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1
  • glutamate decarboxylase 2