Transcription profiling of mouse Bax null versus NGF-Bax double null animals

We report that developmental competition between sympathetic neurons for survival is critically dependent on a sensitization process initiated by target innervation and mediated by a series of feedback loops. Target-derived nerve growth factor (NGF) promoted expression of its receptor TrkA in neurons and prolonged TrkA-mediated signals. NGF also controlled expression of brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4), which, through the receptor p75, can kill neighboring neurons with low retrograde NGF-TrkA signaling whereas neurons with high NGF-TrkA signaling are protected. Perturbation of any of these feedback loops disrupts the dynamics of competition. We suggest that three target-initiated events are essential for rapid and robust competition between neurons: sensitization, paracrine apoptotic signaling, and protection from such effects. Experiment Overall Design: This experiment examine gene expression differences in superior cervical ganglia fro P0 bax null versus NGF-Bax double null animals. The Bax genotype was used in order to prevent the neuronal cell death normally observed in the NGF null animal.本研究证实，交感神经元之间为存活而发生的发育性竞争，其关键依赖于由靶神经支配启动、并通过一系列反馈环路介导的致敏过程。靶源性神经生长因子（nerve growth factor，NGF）可促进神经元内其受体TrkA的表达，并延长TrkA介导的信号通路活性。NGF同时还可调控脑源性神经营养因子（brain derived neurotrophic factor，BDNF）与神经营养因子4（neurotrophin-4，NT4）的表达：二者可通过p75受体，杀死逆向NGF-TrkA信号通路活性较低的邻近神经元，而逆向NGF-TrkA信号通路活性较高的神经元则可获得保护。上述任一反馈环路的扰动，均会破坏神经元竞争的动态平衡。我们提出，靶组织启动的三大事件是神经元间快速且稳定竞争的必要条件：致敏作用、旁分泌凋亡信号传导，以及对这类效应的拮抗保护。实验整体设计：本实验旨在检测出生后0日（P0）Bax基因缺失型与NGF-Bax双基因缺失型动物颈上神经节内的基因表达差异。选用Bax基因缺失型基因型，是为了阻断NGF基因缺失型动物中正常出现的神经元细胞死亡。