The vertebrate ortholog of Aristaless is regulated by Dlx genes in the developing forebrain

Inma Cobos, Vania Broccoli, John L R Rubenstein

Research output: Contribution to journalArticlepeer-review

Abstract

The Dlx transcription factors have a central role in controlling the development of γ-aminobutyric acid (GABA)-ergic neurons in the forebrain. However, little is known about how they control the properties of GABAergic neurons. One candidate is the Aristaless (Arx) homeobox gene, which lies genetically downstream of the fly Dlx gene (Distal-less, Dll). The expression of Arx in the mouse forebrain includes Dlx-expressing territories, such us the ventral thalamus, parts of the hypothalamus, and the ganglionic eminences and their derivatives in the subpallial telencephalon, and is expressed, as with the Dlx genes, in cortical GABAergic neurons. By using gain-of-function and loss-of-function assays in mouse and chicken embryos, we show that the Dlx genes have a conserved role in regulating the expression of Arx in the forebrain of vertebrates. Ectopic expression of Dlx genes with electroporation in brain slices from mouse embryos and in the neural tube of chick embryos shows that Dlx genes are sufficient to induce Arx ectopically. Moreover, we provide evidence that the Dlx genes exert a functionally relevant role in regulating Arx in vivo, as shown by the severe reduction in the expression of Arx in Dlx1/2 double-knockout mice. Therefore, our results suggest evolutionarily conserved functions of Dlx genes in regulating Arx expression between Drosophila and vertebrates.

Original languageEnglish
Pages (from-to)292-303
Number of pages12
JournalJournal of Comparative Neurology
Volume483
Issue number3
DOIs
Publication statusPublished - Mar 14 2005

Keywords

  • Basal ganglia
  • Cortex
  • Epilepsy
  • GABA
  • MGE
  • Migration

ASJC Scopus subject areas

  • Neuroscience(all)

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