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The Journal of Neuroscience, June 1, 2001, 21(11):3904-3910
Target-Derived Neurotrophic Factors Regulate the Death of Developing Forebrain Neurons after a Change in their Trophic Requirements
R. Beau Lotto, Pundit Asavaritikrai, Leila Vali, and David J. Price Genes and Development Group, Department of Biomedical Sciences, University Medical School, Edinburgh EH8 9XD, United Kingdom
Many neurons die as the normal brain develops. How this is regulated and whether the mechanism involves neurotrophic molecules from target cells are unknown. We found that cultured neurons from a key forebrain structure, the dorsal thalamus, develop a need for survival factors including brain-derived neurotrophic factor (BDNF) from their major target, the cerebral cortex, at the age at which they innervate it. Experiments in vivo have shown that rates of dorsal thalamic cell death are reduced by increasing cortical levels of BDNF and are increased in mutant mice lacking functional BDNF receptors or thalamocortical projections; these experiments have also shown that an increase in the rates of dorsal thalamic cell death can be achieved by blocking BDNF in the cortex. We suggest that the onset of a requirement for cortex-derived neurotrophic factors initiates a competitive mechanism regulating programmed cell death among dorsal thalamic neurons.
Key words: brain-derived neurotrophic factor; cerebral cortex; programmed cell death; small eye mice; thalamus; Trk receptors
Copyright © 2001 Society for Neuroscience 0270-6474/01/21113904-07$05.00/0
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