A Model for Neuronal Competition During Development

doi:10.1126/science.1152677

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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

Abstract: We report that developmental competition between sympatheticneurons for survival is critically dependent on a sensitizationprocess initiated by target innervation and mediated by a seriesof feedback loops. Target-derived nerve growth factor (NGF)promoted expression of its own receptor TrkA in mouse and ratneurons and prolonged TrkA-mediated signals. NGF also controlledexpression of brain-derived neurotrophic factor and neurotrophin-4,which, through the receptor p75, can kill neighboring neuronswith low retrograde NGF-TrkA signaling whereas neurons withhigh NGF-TrkA signaling are protected. Perturbation of any ofthese feedback loops disrupts the dynamics of competition. Wesuggest that three target-initiated events are essential forrapid 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.

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

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