CENTRALLY ACTIVE DIFFERENTIATION FACTORS IN THE NERVOUS-SYSTEM

The adult mammalian brain is a remarkably heterogeneous structure comprised of more than 50 biochemically distinct types of neurons. This phenotypic diversity is established during development, not only as the result of genetic but also epigenetic influences. It is believed that extracellular proteins, called differentiation factors, both instruct neurons in their original choice of neurotransmitter substance and, in certain situations, revise those biochemical decisions. The first candidate differentiation factor in the brain has only recently been proposed. This muscle-derived substance has the unique ability, in culture, to initiate expression of genes associated with catecholamine transmitter synthesis in non-catecholamine neurons of the brain. Because it also amplifies expression in cultured catecholamine-producing neurons in vitro and in vivo, it may prove to be an important therapeutic agent in diseases involving catecholamine shortages.