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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Apoptosis
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Brain-Derived Neurotrophic Factor / metabolism
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Cell Survival
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Cells, Cultured
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Computer Simulation
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Feedback, Physiological
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Gene Expression Profiling
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Gene Expression Regulation, Developmental*
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Mathematics
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Mice
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Models, Neurological*
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Nerve Growth Factor / metabolism*
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Nerve Growth Factors / metabolism
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Neurons / cytology
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Neurons / physiology*
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Oligonucleotide Array Sequence Analysis
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Rats
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Receptor, trkA / genetics
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Receptor, trkA / metabolism*
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Receptors, Nerve Growth Factor / genetics
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Receptors, Nerve Growth Factor / metabolism
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Signal Transduction
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Superior Cervical Ganglion / cytology*
Substances
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Brain-Derived Neurotrophic Factor
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Nerve Growth Factors
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Receptors, Nerve Growth Factor
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Ngfr protein, mouse
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Nerve Growth Factor
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Receptor, trkA
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neurotrophin 4