Neurotrophins and the Specification of Neuronal Phenotype

Nerve growth factor, brain derived neurotrophic factor and neurotrophin-3 all influence sensory neurons derived from the dorsal root ganglia. Traditionally these neurotrophins have been thought of as survival factors for sensory neurons during their development. Recent evidence from experiments where the in vivo levels of these proteins has been manipulated indicates that they may influence the development of specific sensory neuron phenotypes. In this review these experiments are discussed in relation to the mechanisms by which neurotrophins could influence the phenotypic fate of sensory neurons. The first mechanism requires that when a neuron becomes dependent for survival on a neurotrophin the availability of the factor simply influences the number of neurons surviving with a certain modality. This model requires that neurotrophin repsonsiveness is a determinant of the possible modalities that the neuron may acquire. The second mechanism requires that the availability of a given neurotrophin influences how many neurons can differentiate into different sensory neuron phenotype independent of survival. The available experimental data is discussed in relation to these two models.