Stabilization of growing retinal axons by the combined signaling of nitric oxide and brain-derived neurotrophic factor

Alan F. Ernst, Gianluca Gallo, Paul C. Letourneau, Steven C. McLoon

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

Abstract

The pattern of axonal projections early in the development of the nervous system lacks the precision present in the adult. During a developmental process of refinement, mistargeted projections are eliminated while correct projections are retained. Previous studies suggest that during development nitric oxide (NO) is involved in the elimination of mistargeted retinal axons, whereas brain-derived neurotrophic factor (BDNF) may stabilize retinal axon arbors. It is unclear whether these neuromodulators interact. This study showed that NO induced growth cone collapse and retraction of developing retinal axons. This effect was not attributable to NO-induced neurotoxicity. BDNF protected growth cones and axons from the effects of NO. This effect was specific to BDNF, because neither nerve growth factor (NGF) nor neurotrophin-3 (NT-3) prevented NO-induced growth cone collapse and axon retraction. Exposure to both BDNF and NO, but not either factor alone, stabilized growth cones and axons. Stabilized axons exhibited minimal retraction or extension. This response appears to be a new axon 'state' and not simply a partial amelioration of the effect of NO, because lower doses of BDNF or NO allowed axon extension. Furthermore, BDNF/NO-induced growth cone stabilization correlated with the appearance of a cytochalasin D-resistant population of actin filaments. BDNF protection from NO likely was mediated locally at the level of the growth cone, because growth cones or individual filopodia in contact with BDNF-coated beads were protected from NO-induced collapse. These findings suggest a cellular mechanism by which some axonal connections are stabilized and some are eliminated during development.

Original languageEnglish (US)
Pages (from-to)1458-1469
Number of pages12
JournalJournal of Neuroscience
Volume20
Issue number4
DOIs
StatePublished - Feb 15 2000

Keywords

  • Actin
  • BDNF
  • Development
  • Growth cones
  • Nitric oxide
  • Retinal axons

Fingerprint Dive into the research topics of 'Stabilization of growing retinal axons by the combined signaling of nitric oxide and brain-derived neurotrophic factor'. Together they form a unique fingerprint.

Cite this