A model for neuronal competition during development.

Authors:
Deppmann CD, Mihalas S, Sharma N, Lonze BE, Niebur E, Ginty DD
Associated Labs:
Ginty Lab (Johns Hopkins University and School of Medicine)
Science. 2008 Apr 18. 320(5874):369-73.
PMID: 18323418
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.

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