Neurotrophic factors in brain development

Neurotrophic factors are target-derived survival factors During nervous system development, neurons are generated in numbers exceeding those found in adults. The surplus neurons are eliminated by programmed cell death. In higher organisms this process is influenced by factors outside the cells themselves, called neurotrophic factors. The discovery of neurotrophic factors goes back to the 1950s, when Rita Levi-Montalcini was investigating the relationship between the nervous system and its peripheral targets. She and her collaborators found that on removal of an organ from a chick embryo, its innervating ganglion neurons were lost as well. Conversely, the addition of an extra target resulted in excessive neuronal survival. She postulated that a soluble factor produced by the target promoted neuronal survival. Eventually this factor was isolated and named nerve growth factor (NGF; Cohen & Levi-Montalcini, 1957). A related protein was purified from pig brain in 1982, and was named brain-derived neurotrophic factor (BDNF; Barde et al ., 1982). With the discovery of BDNF, a family of neurotrophic factors was established: the NGF family of neurotrophic factors, or the neurotrophins. Since then the mammalian branch of the family has been gifted with two additional members, neurotrophin-3 (NT-3) (Hohn et al ., 1990) and NT-4 (Hallbook et al ., 1991). To date several proteins with neurotrophic action have been described. Apart from the neurotrophins, members of the glial cell line-derived (GDNF) factor family are the most important. Neurotrophic factors and their receptors are expressed during development and in adulthood.