Among growth factors, neurotrophins appear to play a critical role particularly in neurite outgrowth and terminal arborization. In addition to their classical role in neuronal differentiation and survival, neurotrophins have been strongly implicated in axon pathfinding.63 The notion that growth factors can guide growing axons to their targets was introduced more than 20 years ago.51 This assumption was confirmed by culture experiments showing that nerve growth factor (NGF) induces a chemotactic response of sensory neurons.31 The growing tip of the axons, the growth cones expresses growth factor receptors. The neurotrophic influence seems to depend on the receptor-mediated uptake and on the retrograde axonal transport toward the soma of the responsive neuron.44,69 In vivo and in vitro experiments led to the hypothesis that growth factors promote the development of innervation. As will be revealed later, the effects of NGF on the development of cholinergic neurons support this idea. However, the concentration of NGF required to produce this effect appears to be higher than endogenous levels of NGF. To explain this paradox, it has been postulated that most of the developing neurons die during embryogenesis, because of their insufficient ability to compete for the limited amount of a trophic factor42,45,24 and undergo synaptic plasticity.66

From Messengers to Molecules: Memories Are Made of These, edited by Gernot Riedel and Bettina Platt. ©2004 and Kluwer Academic / Plenum Publishers.

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