Neurons typically require contact with targets to survive during development, and target organs have been shown to synthesize trophic factors that promote the survival of innervating neurons. During the past few years, the neurotrophins, a family of four trophic factors with overlapping but distinct specificities, have been characterized. Using genetics, we have shown that these genes are essential for normal development, but absence of a single gene product does not result in loss of all classes of neurons responsive to a particular neurotrophin in vitro. Thus there must be redundancy of trophic factors in vivo that permits survival of many neurons. Results also imply that some neurons require more than one neurotrophin to survive during development.
Single neurons appear to depend sequentially on different neurotrophins.
Of particular interest, the neurotrophin NT-3 is capable of supporting survival of many neurons that later become dependent on other factors. NT-3 derived from these cells is essential to enable these neuronal populations to survive long enough to establish contact with their final targets, where they gain access to other trophic factors. Ardem Patapoutian has shown that NT-3 expression is controlled not by the innervating neurons but by interactions between cells in the target regions. He has identified factors that can replace these cellular interactions. Eric Huang has identified a transcription factor involved in regulation of the neurotrophin receptors of the trk receptor tyrosine kinase family.