Jones K R, Reichardt L F
Howard Hughes Medical Institute, University of California-San Francisco 94143.
Proc Natl Acad Sci U S A. 1990 Oct;87(20):8060-4. doi: 10.1073/pnas.87.20.8060.
Cell death within the developing vertebrate nervous system is regulated in part by interactions between neurons and their innervation targets that are mediated by neurotrophic factors. These factors also appear to have a role in the maintenance of the adult nervous system. Two neurotrophic factors, nerve growth factor and brain-derived neurotrophic factor, share substantial amino acid sequence identity. We have used a screen that combines polymerase chain reaction amplification of genomic DNA and low-stringency hybridization with degenerate oligonucleotides to isolate human BDNF and a human gene, neurotrophin-3, that is closely related to both nerve growth factor and brain-derived neurotrophic factor. mRNA products of the brain-derived neurotrophic factor and neurotrophin-3 genes were detected in the adult human brain, suggesting that these proteins are involved in the maintenance of the adult nervous system. Neurotrophin-3 is also expected to function in embryonic neural development.
发育中的脊椎动物神经系统内的细胞死亡部分受神经营养因子介导的神经元与其神经支配靶标之间相互作用的调节。这些因子似乎在成体神经系统的维持中也发挥作用。两种神经营养因子,神经生长因子和脑源性神经营养因子,具有大量的氨基酸序列同一性。我们利用一种将基因组DNA的聚合酶链反应扩增与低严谨度杂交和简并寡核苷酸相结合的筛选方法,分离出了人类脑源性神经营养因子和一个与神经生长因子及脑源性神经营养因子都密切相关的人类基因——神经营养素-3。在成体人类大脑中检测到了脑源性神经营养因子和神经营养素-3基因的mRNA产物,这表明这些蛋白质参与了成体神经系统的维持。神经营养素-3预计也在胚胎神经发育中发挥作用。