Neurotrophins are required for nerve growth during development.
Although the requirement of neurotrophins for the prevention of cell death in the peripheral nervous system is well established, their physiological involvement in nerve growth is still unclear. To address this question, we generated a mouse that expresses the green fluorescent protein in post-mitotic neurons, allowing the repeated visualization of all motor and sensory axons during development. We imaged the growth of these axons into the limb bud of day 10.5 embryos. Sensory axons, but rarely motor axons, were targeted to ectopically placed beads containing any of the neurotrophins NGF, BDNF, NT-3 or NT-4/5. Conversely, a combination of function-blocking monoclonal antibodies to NGF, BDNF and NT-3 dramatically inhibited elongation of both sensory and motor axons in the limb bud, indicating that the growth of mixed nerves is dependent upon neurotrophins during development.
Tucker
K L
KL
Department of Neurobiochemistry, Max Planck Institute of Neurobiology, Am Klopferspitz 18a, 82152 Martinsried, Germany.
Meyer
M
M
Barde
Y A
YA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001369:Axons / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003574:Cytochrome c Group / Q000494:pharmacology; D004337:Drug Carriers; D018878:Limb Buds / Q000196:embryology / Q000254:growth & development / Q000294:innervation; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010525:Peripheral Nerves / Q000187:drug effects / Q000196:embryology / Q000254:growth & development*; D013127:Spinal Nerves
D000911:Antibodies, Monoclonal; D019208:Brain-Derived Neurotrophic Factor; D003574:Cytochrome c Group; D004337:Drug Carriers; D008164:Luminescent Proteins; D009414:Nerve Growth Factors; C071951:neurotrophin 5; D020932:Nerve Growth Factor; C073922:neurotrophin 4