Astroglial-Mediated Remodeling of the Interhemispheric Midline Is Required for the Formation of the Corpus Callosum

Ilan Gobius, Laura Morcom, Rodrigo Suárez, Jens Bunt, Polina Bukshpun, William Reardon, William B. Dobyns, John L.R. Rubenstein, A. James Barkovich, Elliott H. Sherr, Linda J. Richards

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

The corpus callosum is the major axon tract that connects and integrates neural activity between the two cerebral hemispheres. Although ∼1:4,000 children are born with developmental absence of the corpus callosum, the primary etiology of this condition remains unknown. Here, we demonstrate that midline crossing of callosal axons is dependent upon the prior remodeling and degradation of the intervening interhemispheric fissure. This remodeling event is initiated by astroglia on either side of the interhemispheric fissure, which intercalate with one another and degrade the intervening leptomeninges. Callosal axons then preferentially extend over these specialized astroglial cells to cross the midline. A key regulatory step in interhemispheric remodeling is the differentiation of these astroglia from radial glia, which is initiated by Fgf8 signaling to downstream Nfi transcription factors. Crucially, our findings from human neuroimaging studies reveal that developmental defects in interhemispheric remodeling are likely to be a primary etiology underlying human callosal agenesis.

Original languageEnglish
Pages (from-to)735-747
Number of pages13
JournalCell Reports
Volume17
Issue number3
DOIs
StatePublished - Oct 11 2016

Keywords

  • Fgf8
  • Nfia
  • Nfib
  • astrocyte
  • callosal agenesis
  • interhemispheric fissure

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