Investigating the synergistic effect of combined neurotrophic factor concentration gradients to guide axonal growth.
Neurotrophic factors direct axonal growth toward the target tissue by a concentration gradient, which is mediated through different tyrosine kinase cell surface receptors. In this study, well-defined concentration gradients of neurotrophic factors (NFs) allowed us to study the synergistic effect of different NFs (e.g. nerve growth factor [NGF], neurotrophin-3 [NT-3] and brain-derived neurotrophic factor [BDNF]) for axonal guidance of embryonic lumbar dorsal root ganglion cells (DRGs). Effective guidance of DRG axons was achieved with a minimum NGF concentration gradient of 133 ng/ml/mm alone, or combined NGF and NT-3 concentration gradients of 80 ng/ml/mm each. Interestingly, the combined concentration gradients of NGF and BDNF did not show any significant synergism at the concentration gradients studied. The synergism observed between NGF and NT-3 indicates that axons may be guided over a 12.5 mm distance, which is significantly greater than that of 7.5 mm calculated by us for NGF alone or that of 2 mm observed by others.
Cao
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Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ontario, Canada M5S 3E5.
Shoichet
M S
MS
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D009414:Nerve Growth Factors / Q000494:pharmacology*
D004338:Drug Combinations; D009414:Nerve Growth Factors