Dose and age-dependent axonal responses of embryonic trigeminal neurons to localized NGF via p75NTR receptor.
Nerve growth factor (NGF) and related neurotrophins are target-derived survival factors for sensory neurons. In addition, these peptides modulate neuronal differentiation, axon guidance, and synaptic plasticity. We tested axonal behavior of embryonic trigeminal neurons towards localized sources of NGF in collagen gel assays. Trigeminal axons preferentially grow towards lower doses of localized NGF and grow away from higher concentrations at earlier stages of development, but do not show this response later. Dorsal root ganglion axons also show similar responses to NGF, but NGF-dependent superior cervical ganglion axons do not. Such axonal responses to localized NGF sources were also observed in Bax-/- mice, suggesting that the axonal effects are largely independent of cell survival. Immunocytochemical studies indicated that axons, which grow towards or away from localized NGF are TrkA-positive, and TrkA-/- TG axons do not respond to any dose of NGF. We further show that axonal responses to NGF are absent in TG derived from mice that lack the p75 neurotrophin receptor (p75NTR). Collectively, our results suggest that localized sources of NGF can direct axon outgrowth from trigeminal ganglion in a dose- and age-dependent fashion, mediated by p75NTR signaling through TrkA expressing axons.
Department of Cell Biology and Anatomy, LSU Health Sciences Center, 1901 Perdido Street, New Orleans, Louisiana 70112, USA.
P Hande
PH
Ozdinler
Emel
E
Ulupinar
Reha S
RS
Erzurumlu
D000367:Age Factors; D000818:Animals; D001369:Axons / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D048708:Cell Growth Processes / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D011247:Pregnancy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000166:cytology* / Q000196:embryology; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D051028:bcl-2-Associated X Protein; D020932:Nerve Growth Factor; D020917:Receptor, trkA