Méchaly Ilana, Bourane Steeve, Piquemal David, Al-Jumaily Mohammed, Ventéo Stéphanie, Puech Sylvie, Scamps Frédérique, Valmier Jean, Carroll Patrick
I.N.S.E.R.M. U583, Institut des Neurosciences de Montpellier-Hôpital St Eloi. 80, rue Augustin Fliche. BP 74103. 34091 Montpellier cedex 5, France.
Mol Cell Neurosci. 2006 Jul;32(3):217-29. doi: 10.1016/j.mcn.2006.04.004.
In order to shed light on transcriptional networks involved in adult peripheral nerve repair program, we propose for the first time an organization of the transcriptional dynamics of the mouse dorsal root ganglia (DRG) following a sciatic nerve lesion. This was done by a non-hierarchical bioinformatical clustering of four Serial Analysis of Gene Expression libraries performed on DRG at embryonic day E13, neonatal day P0, adult and adult 3 days post-sciatic nerve section. Grouping genes according to their expression profiles shows that a combination of down-regulation of genes expressed at the adult stages, re-expression of embryonic genes and induction of a set of de novo genes takes place in injured neurons. Focusing on this latter event highlights Ddit3, Timm8b and Oazin as potential new injury-induced molecular actors involved in a stress response pathway. Their association with the traumatic state was confirmed by real-time PCR and in situ hybridization investigations. Clustering analysis allows us to distinguish developmental re-programming events from nerve-injury-induced processes and thus provides a basis for molecular understanding of transcriptional alterations taking place in the DRG after a sciatic nerve lesion.
为了阐明参与成人外周神经修复程序的转录网络，我们首次提出了坐骨神经损伤后小鼠背根神经节（DRG）转录动力学的组织方式。这是通过对胚胎期E13、新生期P0、成年期以及坐骨神经切断术后3天的成年小鼠DRG进行的四个基因表达序列分析文库的非层次生物信息聚类来完成的。根据基因表达谱对基因进行分组表明，在受损神经元中发生了成年期表达基因的下调、胚胎基因的重新表达以及一组从头基因的诱导的组合。关注后一事件突出了Ddit3、Timm8b和Oazin作为参与应激反应途径的潜在新的损伤诱导分子参与者。通过实时PCR和原位杂交研究证实了它们与创伤状态的关联。聚类分析使我们能够区分发育重编程事件和神经损伤诱导的过程，从而为分子理解坐骨神经损伤后DRG中发生的转录改变提供了基础。
