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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