Age-related changes underlie switch in netrin-1 responsiveness as growth cones advance along visual pathway

Derryck Shewan, A. Dwivedy, R. Anderson, C. Holt

Research output: Contribution to journalArticlepeer-review

162 Citations (Scopus)

Abstract

Retinal axons are led out of the eye by netrin-1, an attractive guidance cue which is secreted at the optic nerve head. In the optic pathway, however, netrin-1 is expressed in areas that exclude retinal axon growth. This suggests that axons may change in their responsiveness to netrin-1 as they advance along the pathway. Indeed, in our 'whole-pathway' preparation in Xenopus, a gradual change from attraction to repulsion occurred as retinal axons emerged from progressively distal points along the pathway. We also found that axons that were aged in culture without pathway experience underwent a similar change, which correlated with a decline in cyclic AMP (cAMP) and netrin-1 receptor expression. Cyclic AMP elevators and adenosine A2b receptor agonists rejuvenated the behavior of old growth cones, causing them to regain attraction to netrin-1, whereas antagonists caused young growth cones to be repelled. These findings show that netrin-1 responsiveness is developmentally regulated and suggest that intrinsic changes that lower cAMP levels underlie this regulation.

Original languageEnglish
Pages (from-to)955-962
Number of pages7
JournalNature Neuroscience
Volume5
DOIs
Publication statusPublished - Sept 2002

Keywords

  • ADENOSINE A2B RECEPTOR
  • AXON GUIDANCE
  • CYCLIC-AMP
  • EXPRESSION
  • DCC
  • XENOPUS
  • NEURONS
  • DIFFERENTIATION
  • GLYCOPROTEIN
  • REGENERATION

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