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 journalArticle

148 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 - Sep 2002

Keywords

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

Cite this

Age-related changes underlie switch in netrin-1 responsiveness as growth cones advance along visual pathway. / Shewan, Derryck; Dwivedy, A.; Anderson, R.; Holt, C.

In: Nature Neuroscience, Vol. 5, 09.2002, p. 955-962.

Research output: Contribution to journalArticle

@article{0c2309e66f79426b8a8388eeac4cbbc8,
title = "Age-related changes underlie switch in netrin-1 responsiveness as growth cones advance along visual pathway",
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.",
keywords = "ADENOSINE A2B RECEPTOR, AXON GUIDANCE, CYCLIC-AMP, EXPRESSION, DCC, XENOPUS, NEURONS, DIFFERENTIATION, GLYCOPROTEIN, REGENERATION",
author = "Derryck Shewan and A. Dwivedy and R. Anderson and C. Holt",
year = "2002",
month = "9",
doi = "10.1038/nn919",
language = "English",
volume = "5",
pages = "955--962",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Age-related changes underlie switch in netrin-1 responsiveness as growth cones advance along visual pathway

AU - Shewan, Derryck

AU - Dwivedy, A.

AU - Anderson, R.

AU - Holt, C.

PY - 2002/9

Y1 - 2002/9

N2 - 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.

AB - 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.

KW - ADENOSINE A2B RECEPTOR

KW - AXON GUIDANCE

KW - CYCLIC-AMP

KW - EXPRESSION

KW - DCC

KW - XENOPUS

KW - NEURONS

KW - DIFFERENTIATION

KW - GLYCOPROTEIN

KW - REGENERATION

U2 - 10.1038/nn919

DO - 10.1038/nn919

M3 - Article

VL - 5

SP - 955

EP - 962

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

ER -