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ReportsA Model for Neuronal Competition During Development
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.
1 The Solomon Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. * These authors contributed equally to this work.
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Science. ISSN 0036-8075 (print), 1095-9203 (online)
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