DRAXIN regulates interhemispheric fissure remodelling to influence the extent of corpus callosum formation

Laura Morcom, Timothy J. Edwards, Eric Rider, Dorothy Jones-Davis, Jonathan Wc Lim, Kok Siong Chen, Ryan J. Dean, Jens Bunt, Yunan Ye, Ilan Gobius, Rodrigo Suárez, Simone Mandelstam, Elliott H. Sherr, Linda J. Richards

Research output: Contribution to journalArticlepeer-review

Abstract

Corpus callosum dysgenesis (CCD) is a congenital disorder that incorporates either partial or complete absence of the largest cerebral commissure. Remodelling of the interhemispheric fissure (IHF) provides a substrate for callosal axons to cross between hemispheres, and its failure is the main cause of complete CCD. However, it is unclear whether defects in this process could give rise to the heterogeneity of expressivity and phenotypes seen in human cases of CCD. We identify incomplete IHF remodelling as the key structural correlate for the range of callosal abnormalities in inbred and outcrossed BTBR mouse strains, as well as in humans with partial CCD. We identify an eight base-pair deletion in Draxin and misregulated astroglial and leptomeningeal proliferation as genetic and cellular factors for variable IHF remodelling and CCD in BTBR strains. These findings support a model where genetic events determine corpus callosum structure by influencing leptomeningeal-astroglial interactions at the IHF.

Original languageEnglish
Article numbere61618
JournaleLife
Volume10
DOIs
StatePublished - May 4 2021

Keywords

  • astroglia
  • axon guidance
  • cerebral cortex
  • corpus callosum
  • Draxin
  • human
  • midline
  • mouse
  • neuroscience

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