Target-derived neurotrophic factors regulate the death of developing forebrain neurons after a change in their trophic requirements.
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.
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Genes and Development Group, Department of Biomedical Sciences, University Medical School, Edinburgh EH8 9XD, United Kingdom.
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D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005136:Eye Proteins; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D009434:Neural Pathways / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D020813:Receptor, trkB / Q000172:deficiency / Q000235:genetics; D020812:Receptor, trkC / Q000172:deficiency / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D013787:Thalamic Nuclei / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D013788:Thalamus / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism
D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D017077:Culture Media, Conditioned; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009414:Nerve Growth Factors; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D017475:Receptors, Nerve Growth Factor; D012097:Repressor Proteins; D020813:Receptor, trkB; D020812:Receptor, trkC