Finn T P, Kim S, Nishi R
Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland 97201, USA.
J Neurobiol. 1998 Feb 15;34(3):283-93.
Ciliary ganglion (CG) neurons undergo target-dependent cell death during embryonic development. Although ciliary neurotrophic factor (CNTF) was identified in vitro by its ability to support the survival of chick CG neurons, its function as a target-derived neurotrophic factor has been questioned by those working on mammalian-derived forms of CNTF. We have purified and cloned a chicken CNTF [chCNTF; formerly growth-promoting activity (GPA)] that is expressed in CG targets during the period of cell death and is secreted by cells transfected with chCNTF. In the present study we used a retroviral vector, RCASBP(A), to overexpress chCNTF in CG target tissues. Elevation of chCNTF biological activity three- to fourfold in the embryonic eye rescued an average of 31% of the neurons that would have normally died in vivo. In some individuals, nearly all of the neurons were rescued. ChCNTF had no effect on the number of neurons observed prior to cell death, nor were there any deleterious effects of either viral infection or overexpression of CNTF. These results show that chCNTF is able to function in vivo as a trophic factor for CG neurons, and suggest that limited availability of trophic support is one of the factors regulating CG neuron survival during development.
睫状神经节（CG）神经元在胚胎发育过程中会经历靶标依赖性细胞死亡。尽管睫状神经营养因子（CNTF）在体外通过其支持鸡CG神经元存活的能力而被鉴定出来，但其作为靶标衍生神经营养因子的功能却受到了研究哺乳动物来源形式的CNTF的人员的质疑。我们已经纯化并克隆了一种鸡CNTF [chCNTF；以前称为生长促进活性（GPA）]，它在细胞死亡期间在CG靶标中表达，并由转染了chCNTF的细胞分泌。在本研究中，我们使用逆转录病毒载体RCASBP（A）在CG靶标组织中过表达chCNTF。胚胎眼中chCNTF生物活性提高三到四倍，平均挽救了31%原本在体内会正常死亡的神经元。在一些个体中，几乎所有神经元都被挽救了。ChCNTF对细胞死亡前观察到的神经元数量没有影响，病毒感染或CNTF过表达也没有任何有害影响。这些结果表明，chCNTF能够在体内作为CG神经元的营养因子发挥作用，并表明营养支持的有限可用性是调节发育过程中CG神经元存活的因素之一。
