Wyatt S, Piñon L G, Ernfors P, Davies A M
School of Biological and Medical Sciences, University of St Andrews, Fife, UK.
EMBO J. 1997 Jun 2;16(11):3115-23. doi: 10.1093/emboj/16.11.3115.
Several in vitro and in vivo studies have led to the widely accepted view that NT3 is required for sympathetic neuroblast survival, induction of TrkA expression and the acquisition of NGF dependence. However, we show that the number of neurons and the levels of trkA and p75 mRNAs in the superior cervical sympathetic ganglion (SCG) of NT3-/- mouse embryos increase normally up to E16, 2 days after SCG neurons start responding to NGF. At E18 and in the postnatal period, there are significant reductions in the number of SCG neurons and in the levels of trkA and p75 mRNAs. These results show that the neurotrophin survival requirements of SCG neurons do not switch from NT3 to NGF during development and that NT3 is not required for the expression of TrkA and p75 and the acquisition of NGF dependence. Rather, some sympathetic neurons have a late requirement for NT3 at the time when they also depend on NGF for survival. The expression of transcripts encoding catalytic TrkC is negligible at this stage, suggesting that NT3 acts mainly via TrkA.
多项体外和体内研究得出了一个被广泛接受的观点,即神经营养因子3(NT3)对于交感神经母细胞的存活、酪氨酸激酶受体A(TrkA)表达的诱导以及对神经生长因子(NGF)依赖性的获得是必需的。然而,我们发现,在NT3基因敲除小鼠胚胎的颈上神经节(SCG)中,神经元数量以及TrkA和p75 mRNA水平在胚胎第16天(即SCG神经元开始对NGF作出反应2天后)之前正常增加。在胚胎第18天及出生后阶段,SCG神经元数量以及TrkA和p75 mRNA水平显著降低。这些结果表明,在发育过程中,SCG神经元对神经营养因子的存活需求不会从NT3转换为NGF,并且NT3对于TrkA和p75的表达以及对NGF依赖性的获得并非必需。相反,一些交感神经元在依赖NGF存活时对NT3有后期需求。在此阶段,编码催化型TrkC的转录本表达可忽略不计,这表明NT3主要通过TrkA发挥作用。