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A model for neuronal competition during development.

ABSTRACT: We report that developmental competition between sympathetic neurons for survival is critically dependent on a sensitization process initiated by target innervation and mediated by a series of feedback loops. Target-derived nerve growth factor (NGF) promoted expression of its own receptor TrkA in mouse and rat neurons and prolonged TrkA-mediated signals. NGF also controlled expression of brain-derived neurotrophic factor and neurotrophin-4, which, through the receptor p75, can kill neighboring neurons with low retrograde NGF-TrkA signaling whereas neurons with high NGF-TrkA signaling are protected. Perturbation of any of these feedback loops disrupts the dynamics of competition. We suggest that three target-initiated events are essential for rapid and robust competition between neurons: sensitization, paracrine apoptotic signaling, and protection from such effects.

SUBMITTER: Deppmann CD

PROVIDER: S-EPMC3612357 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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A model for neuronal competition during development.

Deppmann Christopher D CD Mihalas Stefan S Sharma Nikhil N Lonze Bonnie E BE Niebur Ernst E Ginty David D DD

Science (New York, N.Y.) 20080306 5874

We report that developmental competition between sympathetic neurons for survival is critically dependent on a sensitization process initiated by target innervation and mediated by a series of feedback loops. Target-derived nerve growth factor (NGF) promoted expression of its own receptor TrkA in mouse and rat neurons and prolonged TrkA-mediated signals. NGF also controlled expression of brain-derived neurotrophic factor and neurotrophin-4, which, through the receptor p75, can kill neighboring n ...[more]

PMID: 18323418

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