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Science 320 (5874): 369-373

Copyright © 2008 by the American Association for the Advancement of Science

A Model for Neuronal Competition During Development

Christopher D. Deppmann,1,2* Stefan Mihalas,1,3* Nikhil Sharma,1,2* Bonnie E. Lonze,1,2 Ernst Niebur,1,3 David D. Ginty1,2{dagger}

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.

1 The Solomon Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
2 Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD21205, USA.
3 The Zanvyl Krieger Mind/Brain Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: dginty{at}jhmi.edu


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