Jones and Reichardt (1990) noted that during normal vertebral development, up to 80% of the neurons in diverse cell populations within the forming nervous system die. This is thought to be a mechanism that ensures that adequate numbers of neurons establish appropriate innervation densities with effector organs or other neuronal populations. In several instances, the innervation target of a population of neurons has been shown to have a crucial role in regulating the number of surviving neurons. Targets of neuronal innervation produce a limited supply of neurotrophic factors, and competition between neurons responsive to these factors determines which neurons survive. In addition to nerve growth factor (NGF; 162030), BDNF has been purified and shown in vivo to reduce the amount of naturally occurring neuronal cell death in portions of the peripheral nervous system (Hofer and Barde, 1988). Jones and Reichardt (1990) cloned human BDNF, which encodes a deduced 247 preproprotein that is proteolytically processed into a mature 119-amino acid protein. The mature BDNF protein shares 100% identity with mature porcine Bdnf and 52% identity with mature human NGF. Northern blot analysis detected BDNF transcripts of 1.6 and 4.0 kb in all brain regions examined. Maisonpierre et al. (1991) cloned the human and rat genes encoding BDNF. They demonstrated that the mature form was identical in all mammals examined. Furthermore, the tissue distributions and neuronal specificities are conserved among mammals. By database analysis and RT-PCR, Liu et al. (2005) identified 9 alternatively spliced BDNF transcripts. The transcripts differ in their use of alternative promoters, alternative splice donor and acceptor sites, and alternative polyadenylation sites. Most transcripts encode the previously identified proBDNF; however, 2 transcripts contain additional in-frame methionines that may result in proteins with longer N termini, and another transcript encodes a protein with an internal deletion of 48 amino acids. RT-PCR revealed a complex pattern of BDNF transcripts in brain and a more simple pattern of expression in peripheral tissues. Liu et al. (2005) also identified noncoding RNAs transcribed from a gene that overlaps with BDNF on the opposite strand (BDNFOS; 611468). By in silico analysis, RT-PCR of adult frontal cerebral cortex, medulla, and hippocampus total RNA, and 5-prime RACE of adult hippocampus and cerebellum RNA, Pruunsild et al. (2007) identified numerous BDNF transcripts. The transcripts differ in the length of their 5-prime UTR, and most encode proBDNF. RT-PCR detected tissue-specific expression of BDNF variants. Most showed highest expression in brain, although several alternative transcripts showed relatively high expression in nonneural tissues. The BDNF variants showed variable expression in all specific brain regions examined, and all were expressed at high levels in mammillary body, pons, hippocampus, frontal cortex, colliculi, and olfactory tract. By examining expression of Bdnf transcripts in rat and mouse brain, An et al. (2008) found that mRNAs with short 3-prime UTRs were restricted to somata, whereas those with long 3-prime UTRs also localized to dendrites.