Trophic factors: An evolutionary cul-de-sac or door into higher neuronal function?

Trophic factors, such as the neurotrophins, CNTF, and GDNF, represent unique families of proteins that are essential for the development of the vertebrate nervous system. Surprisingly, there is little evidence to date that these proteins exist in Drosophila melanogaster and Caenorhabditis elegans, even though other polypeptide growth factors, such as EGF, FGF, and insulin, are conserved in these species. For the neurotrophins, the evolution of NGF, BDNF, NT-3, and NT-4 as a family implies that these signaling molecules may be involved in mediating additional neural activities, such as learning, memory, and behavior. Indeed, there is abundant evidence now that BDNF is involved in synapse modification, neurotransmitter release, long-term potentiation, and mechanosensation. The widening scope of neurotrophin action will require more physiological, genomic, and integrative approaches to understand fully the mechanisms by which survival factors can mediate so many diverse effects.