Comparison of SCG expression profiles from Bax null versus NGF-Bax double null mice

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 receptor TrkA in neurons and prolonged TrkA-mediated signals. NGF also controlled expression of brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4), which, through the receptor p75, can kill neighboring neurons with low retrograde NGFTrkA signaling whereas neurons with high NGFTrkA 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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Deppmann CD, Mihalas S, Sharma N, Lonze BE, Niebur E, Ginty DD