The complexity and remarkable specificity found in the nervous system chalÂ lenge the investigator to identify molecular mechanisms guiding neuronal development. Cell-cell interactions mediated by diffusible substances have frequently been suggested to play an important role. Studies on naturally occurring cell death in the nervous system provided early evidence for such interactions by demonstrating that neuronal survival beyond a critical period in development requires interaction between the neurons and the postsynaptic target tissue (for a review see Oppenheim 1981). The discovery of Nerve Growth Factor (NGF) raised the possibility that neuronal development, includÂ ing target-dependent neuronal survival, might be mediated by diffusible moleÂ cules. NGF can be isolated as a 140,000 dalton protein complex ( 7S NGF) of heterologous subunits or as a 26,500 dalton component (beta-NGF) containing two identical polypeptide chains. Experiments in vivo indicate that NGF can reverse naturally occurring as well as experimentally induced cell death in sympathetic and sensory neurons; moreover, anti-NGF antibodies in vivo can block the development of the s ympatheti c nervous system (for reviews see Thoenen & Barde 1980, Hamburger et al 1981, Levi-Monta1cini 1982). That NGF might also influence the choice of targets contacted by neurons is suggested by
Annual Review of Neuroscience – Annual Reviews
Published: Mar 1, 1984
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