Molecular regulation of the developing commissural plate

Randal X. Moldrich, Ilan Gobius, Thomas Pollak, Jiangyang Zhang, Tianbo Ren, Lucia Brown, Susumu Mori, Camino De Juan Romero, Olga Britanova, Victor Tarabykin, Linda J. Richards

Research output: Contribution to journalArticlepeer-review

Abstract

Coordinated transfer of information between the brain hemispheres is essential for function and occurs via three axonal commissures in the telencephalon: the corpus callosum (CC), hippocampal commissure (HC), and anterior commissure (AC). Commissural malformations occur in over 50 human congenital syndromes causing mild to severe cognitive impairment. Disruption of multiple commissures in some syndromes suggests that common mechanisms may underpin their development. Diffusion tensor magnetic resonance imaging revealed that forebrain commissures crossed the midline in a highly specific manner within an oblique plane of tissue, referred to as the commissural plate. This specific anatomical positioning suggests that correct patterning of the commissural plate may influence forebrain commissure formation. No analysis of the molecular specification of the commissural plate has been performed in any species; therefore, we utilized specific transcription factor markers to delineate the commissural plate and identify its various subdomains. We found that the mouse commissural plate consists of four domains and tested the hypothesis that disruption of these domains might affect commissure formation. Disruption of the dorsal domains occurred in strains with commissural defects such as Emx2 and Nfia knockout mice but commissural plate patterning was normal in other acallosal strains such as SatB2-/-. Finally, we demonstrate an essential role for the morphogen Fgf8 in establishing the commissural plate at later developmental stages. The results demonstrate that correct patterning of the commissural plate is an important mechanism in forebrain commissure formation.

Original languageEnglish (US)
Pages (from-to)3645-3661
Number of pages17
JournalJournal of Comparative Neurology
Volume518
Issue number18
DOIs
StatePublished - Sep 15 2010

Keywords

  • Commissural plate
  • Empty spiracles homeobox (Emx)
  • Fibroblast growth factor 8 (Fgf8)
  • Nuclear factor I (Nfi)
  • Sine oculis-related homeobox 3 homolog (Six3)
  • Zinc finger protein of the cerebellum 2 (Zic2)

ASJC Scopus subject areas

  • Neuroscience(all)

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