在小鼠皮层发育过程中，FoxO6影响Plxna4介导的神经元迁移。
FoxO6 affects Plxna4-mediated neuronal migration during mouse cortical development.
作者信息
Paap Ricardo H, Oosterbroek Saskia, Wagemans Cindy M R J, von Oerthel Lars, Schellevis Raymond D, Vastenhouw-van der Linden Annemarie J A, Groot Koerkamp Marian J A, Hoekman Marco F M, Smidt Marten P
机构信息
Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The Netherlands.
Brain Center Rudolf Magnus, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
出版信息
Proc Natl Acad Sci U S A. 2016 Nov 8;113(45):E7087-E7096. doi: 10.1073/pnas.1609111113. Epub 2016 Oct 24.
The forkhead transcription factor FoxO6 is prominently expressed during development of the murine neocortex. However, its function in cortical development is as yet unknown. We now demonstrate that cortical development is altered in and mice, showing migrating neurons halted in the intermediate zone. Using a -directed siRNA approach, we substantiate the requirement of FoxO6 for a correct radial migration in the developing neocortex. Subsequent genome-wide transcriptome analysis reveals altered expression of genes involved in cell adhesion, axon guidance, and gliogenesis upon silencing of We then show that FoxO6 binds to DAF-16-binding elements in the () promoter region and affects expression. Finally, ectopic expression restores radial migration in and siRNA-mediated knockdown models. In conclusion, the presented data provide insights into the molecular mechanisms whereby transcriptional programs drive cortical development.
叉头转录因子FoxO6在小鼠新皮质发育过程中显著表达。然而，其在皮质发育中的功能尚不清楚。我们现在证明，在FoxO6基因敲除和条件性敲除小鼠中皮质发育发生改变，表现为迁移神经元停滞在中间带。使用针对FoxO6的小干扰RNA方法，我们证实了FoxO6对于发育中的新皮质中正确的径向迁移是必需的。随后的全基因组转录组分析揭示，在FoxO6沉默后，参与细胞黏附、轴突导向和神经胶质生成的基因表达发生改变。然后我们表明，FoxO6与DAB1（Disabled homolog 1）启动子区域中的DAF-16结合元件结合，并影响DAB1表达。最后，异位表达DAB1可恢复FoxO6基因敲除和小干扰RNA介导的敲低模型中的径向迁移。总之，所呈现的数据为转录程序驱动皮质发育的分子机制提供了见解。
Zotero 插件