Acute Morphogenic and Chemotropic Effects of Neurotrophins on Cultured EmbryonicXenopusSpinal Neurons

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Abstract
Neurotrophins constitute a family of trophic factors with profound effects on the survival and differentiation of the nervous system. Addition of brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3), but not nerve growth factor (NGF), increased the survival of embryonicXenopusspinal neurons in culture, although all three neurotrophins enhanced neurite outgrowth. Here we report that neurotrophins also exert acute actions on the morphology and motility of 1-day-old culturedXenopusspinal neurons. Bath application of BDNF induced extensive formation of lamellipodia simultaneously at multiple sites along the neurite shaft as well as at the growth cone. The BDNF-induced lamellipodia appeared within minutes, rapidly protruded to their greatest extent in about 10 min, and gradually disappeared thereafter, leaving behind newly formed thin lateral processes. When applied as microscopic concentration gradients, both BDNF and NT-3, but not NGF, induced the growth cone to grow toward the neurotrophin source. Our results suggest that neurotrophic factors, when delivered to responsive neurons, may serve as morphogenic and chemotropic agents during neuronal development.