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 neurotrop hin family of proteins, which support the survival and induce differen tiation of vertebrate neurons. We have studied the effects of neurotro phins on growth cones of embryonic sensory neurons. BDNF and NT-4/5 ca use growth cone collapse and transient neurite growth inhibition in NG F-dependent or NT-3-dependent rat dorsal root ganglion (DRG) neurons b ut 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 neurotr ophins 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 chem oattractants 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 gr owth cones of NGF-dependent or NT-3-dependent neurons, and a reorganiz ation of microfilaments. BDNF induces a rapid transient 3-fold to 4-fo ld increase of F-actin concentration at the central part of growth con es of NGF-dependent neurons. Our results suggest that different neurot rophins have chemoattractive or inhibitory effects on the same growth cone, and that they may act as specific growth cone guidance cues.