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Neurotrophic hypothesis

a hypothesis that arose from studies of nerve growth factor (NGF), the founder of the family of secreted proteins neurotrophin. Its basic principle is that the survival of developing neurons depends on the presence of neurotrophic factor, synthesized in limited quantities in target fields. However, the neurotrophic hypothesis has been extended by demonstrating that the survival of certain populations of neurons is regulated by several neurotrophic factors. For example, some neurons depend on several different neurotrophic factors that can act simultaneously or sequentially during the innervation of the target field. In addition, there are aspects of the action of neurotrophins that do not agree with the classical neurotrophic hypothesis. For example, the dependence of some populations of sensory neurons on certain neurotrophins prior to the occurrence of significant neuronal death suggests that the supply of these neurotrophins is not limiting to survival at this stage of development. There is also evidence that in the stages before and after sensory neurons become dependent on neurotrophins produced by targets, neurotrophins act on at least some sensory neurons in an autocrine way. Nevertheless, despite the growing body of information about the multiple roles and mechanisms of action of neurotrophic factors, the neurotrophic hypothesis remains the best explanation for how neuronal target fields in the developing peripheral nervous system regulate their innervation density.