Birren S J, Lo L, Anderson D J
Division of Biology 216-76, California Institute of Technology, Pasadena 91125.
Development. 1993 Nov;119(3):597-610. doi: 10.1242/dev.119.3.597.
Sympathetic neurons require NGF for survival, but it is not known when these cells first become dependent on neurotrophic factors. We have examined in vitro mitotically active sympathetic neuroblasts immuno-isolated from different embryonic stages, and have correlated this functional data with the expression of neurotrophin receptor mRNAs in vivo. Cells from E14.5 ganglia are supported by neurotrophin-3 (NT-3) in a serum-free medium, but not by NGF; NT-3 acts as a bona fide survival factor for these cells and not simply as a mitogen. By birth, sympathetic neurons are well-supported by NGF, whereas NT-3 supports survival only weakly and at very high doses. This change in neurotrophin-responsiveness is correlated with a reciprocal switch in the expression of trkC and trkA mRNAs by sympathetic neuroblasts in vivo. These data suggest that neurotrophic factors may control neuronal number at earlier stages of development than previously anticipated. They also suggest that the acquisition of NGF-dependence may occur, at least in part, through the loss of receptors for these interim survival factors.
交感神经元的存活需要神经生长因子（NGF），但这些细胞何时首次开始依赖神经营养因子尚不清楚。我们研究了从不同胚胎阶段免疫分离出的体外有丝分裂活跃的交感神经母细胞，并将这些功能数据与体内神经营养因子受体mRNA的表达相关联。来自E14.5神经节的细胞在无血清培养基中由神经营养因子-3（NT-3）支持，但不由NGF支持；NT-3对这些细胞起到真正的存活因子作用，而不仅仅是有丝分裂原。到出生时，交感神经元得到NGF的良好支持，而NT-3仅在非常高的剂量下才对存活有微弱支持。神经营养因子反应性的这种变化与体内交感神经母细胞中trkC和trkA mRNA表达的相互转换相关。这些数据表明，神经营养因子可能在比先前预期更早的发育阶段控制神经元数量。它们还表明，对NGF依赖性的获得可能至少部分是通过这些临时存活因子受体的丧失而发生的。
