Neurotrophins as in vitro growth cone guidance molecules for embryonic sensory neurons.

Neurotrophins NGF, BDNF, NT-3, and NT-4/5 are members of the neurotrophin family of proteins, which support the survival and induce differentiation of vertebrate neurons. We have studied the effects of neurotrophins on growth cones of embryonic sensory neurons. BDNF and NT-4/5 cause growth cone collapse and transient neurite growth inhibition in NGF-dependent or NT-3-dependent rat dorsal root ganglion (DRG) neurons but not in BDNF-dependent or NT-4/5-dependent neurons, whereas NGF and NT-3 do not produce growth-cone collapse in these neurons. All neurotrophins show a chemoattractive effect on growth cones of embryonic DRG neurons: NGF and NT-3 are chemoattractants for all DRG neurons, except NT-3-dependent and NT-4/5-dependent neurons; BDNF and NT-4/5 are chemoattractants only for BDNF-dependent DRG neurons. BDNF-induced and NT-4/5-induced growth cone collapse is quantitatively characterized as a 50% decrease in F-actin content, total protein content, and area of growth cones of NGF-dependent or NT-3-dependent neurons, and a reorganization of microfilaments. BDNF induces a rapid transient 3-fold to 4-fold increase of F-actin concentration at the central part of growth cones of NGF-dependent neurons. Our results suggest that different neurotrophins have chemoattractive or inhibitory effects on the same growth cone, and that they may act as specific growth cone guidance cues.