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Distinct molecular pathways for development of telencephalic interneuron subtypes revealed through analysis of Lhx6 mutants.

Here we analyze the role of the Lhx6 lim-homeobox transcription factor in regulating the development of subsets of neocortical, hippocampal, and striatal interneurons. An Lhx6 loss-of-function allele, which expresses placental alkaline phosphatase (PLAP), allowed analysis of the development and fate of Lhx6-expressing interneurons in mice lacking this homeobox transcription factor. There are Lhx6+;Dlx+ and Lhx6-;Dlx+ subtypes of tangentially migrating interneurons. Most interneurons in Lhx6(PLAP/PLAP) mutants migrate to the cortex, although less efficiently, and exhibit defects in populating the marginal zone and superficial parts of the neocortical plate. By contrast, migration to superficial parts of the hippocampus is not seriously affected. Furthermore, whereas parvalbumin+ and somatostatin+ interneurons do not differentiate, NPY+ interneurons are present; we suggest that these NPY+ interneurons are derived from the Lhx6-;Dlx+ subtype. Striatal interneurons show deficits distinct from pallial interneurons, including a reduction in the NPY+ subtype. We provide evidence that Lhx6 mediates these effects through promoting expression of receptors that regulate interneuron migration (ErbB4, CXCR4, and CXCR7), and through promoting the expression of transcription factors either known (Arx) or implicated (bMaf, Cux2, and NPAS1) in controlling interneuron development.

Pubmed ID: 18613121


  • Zhao Y
  • Flandin P
  • Long JE
  • Cuesta MD
  • Westphal H
  • Rubenstein JL


The Journal of comparative neurology

Publication Data

September 1, 2008

Associated Grants

  • Agency: NIMH NIH HHS, Id: K05 MH065670
  • Agency: NIMH NIH HHS, Id: K05 MH065670
  • Agency: NIMH NIH HHS, Id: K05 MH065670-05
  • Agency: NIMH NIH HHS, Id: R01 MH081880
  • Agency: NIMH NIH HHS, Id: R01 MH49428-01
  • Agency: NIMH NIH HHS, Id: R37 MH049428
  • Agency: Intramural NIH HHS, Id:

Mesh Terms

  • Animals
  • Animals, Newborn
  • Cell Differentiation
  • Cell Movement
  • Cerebral Cortex
  • Corpus Striatum
  • Embryo, Mammalian
  • Hippocampus
  • Homeodomain Proteins
  • Interneurons
  • LIM-Homeodomain Proteins
  • Mice
  • Mice, Inbred Strains
  • Mutation
  • Neocortex
  • Nerve Tissue Proteins
  • Telencephalon
  • Transcription Factors