Netrin-DCC signaling regulates corpus callosum formation through attraction of pioneering axons and by modulating slit2-mediated repulsion

Thomas Fothergill, Amber Lee S. Donahoo, Amelia Douglass, Oressia Zalucki, Jiajia Yuan, Tianzhi Shu, Geoffrey J. Goodhill, Linda J. Richards

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

The left and right sides of the nervous system communicate via commissural axons that cross the midline during development using evolutionarily conserved molecules. These guidance cues have been particularly well studied in the mammalian spinal cord, but it remains unclear whether these guidance mechanisms for commissural axons are similar in the developing forebrain, in particular for the corpus callosum, the largest and most important commissure for cortical function. Here, we show that Netrin1 initially attracts callosal pioneering axons derived from the cingulate cortex, but surprisingly is not attractive for the neocortical callosal axons that make up the bulk of the projection. Instead, we show that Netrin-deleted in colorectal cancer signaling acts in a fundamentally different manner, to prevent the Slit2-mediated repulsion of precrossing axons thereby allowing them to approach and cross the midline. These results provide the first evidence for how callosal axons integrate multiple guidance cues to navigate the midline.

Original languageEnglish
Pages (from-to)1138-1151
Number of pages14
JournalCerebral Cortex
Volume24
Issue number5
DOIs
StatePublished - May 2014

Keywords

  • DCC
  • Robo1
  • axon guidance
  • commissure formation
  • corpus callosum
  • cortical development
  • neocortex
  • silencing

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