Kajimura Daisuke, Dragomir Cecilia, Ramirez Francesco, Laub Friedrich
Child Health Institute of New Jersey, UMDNJ-Robert Wood Johnson Medical School, 89 French Street, New Brunswick, NJ 08901, United States.
Gene. 2007 Feb 15;388(1-2):34-42. doi: 10.1016/j.gene.2006.09.027. Epub 2006 Oct 10.
Gene targeting in mice has recently demonstrated that transcription factor KLF7 plays a critical role in neurite outgrowth and neuronal survival. Here we extended this genetic evidence by establishing the transcriptional profile of differentiating olfactory sensory neurons (OSNs) in Klf7(-/-) mice, and by identifying relevant genes that are directly regulated by KLF7. Functional clustering of DNA microarray data revealed that loss of KLF7 affects primarily the activity of genes involved in OSN differentiation, axonal growth, cytoskeletal dynamics, cell adhesion and synaptogenesis. Cell transfection experiments, on the other hand, demonstrated that the promoters of the genes encoding the OSN-specific OMP and the adhesion molecule L1 are both activated by KLF7 binding to CACCC motifs. Collectively, these results advance knowledge of transcriptional regulation of olfactory neurogenesis and KLF7 action.
小鼠中的基因靶向研究最近表明,转录因子KLF7在神经突生长和神经元存活中起关键作用。在此,我们通过建立Klf7(-/-)小鼠中分化的嗅觉感觉神经元(OSN)的转录谱,并鉴定由KLF7直接调控的相关基因,扩展了这一遗传学证据。DNA微阵列数据的功能聚类显示,KLF7的缺失主要影响参与OSN分化、轴突生长、细胞骨架动力学、细胞粘附和突触形成的基因的活性。另一方面,细胞转染实验表明,编码OSN特异性OMP和粘附分子L1的基因的启动子均被KLF7与CACCC基序的结合所激活。这些结果共同推进了对嗅觉神经发生转录调控和KLF7作用的认识。