Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Proc Natl Acad Sci U S A. 2011 Sep 6;108(36):14950-5. doi: 10.1073/pnas.1112213108. Epub 2011 Aug 22.
Characterizing the genetic programs that specify development and evolution of the cerebral cortex is a central challenge in neuroscience. Stem cells in the transient embryonic ventricular and subventricular zones generate neurons that migrate across the intermediate zone to the overlying cortical plate, where they differentiate and form the neocortex. It is clear that not one but a multitude of molecular pathways are necessary to progress through each cellular milestone, yet the underlying transcriptional programs remain unknown. Here, we apply differential transcriptome analysis on microscopically isolated cell populations, to define five transcriptional programs that represent each transient embryonic zone and the progression between these zones. The five transcriptional programs contain largely uncharacterized genes in addition to transcripts necessary for stem cell maintenance, neurogenesis, migration, and differentiation. Additionally, we found intergenic transcriptionally active regions that possibly encode unique zone-specific transcripts. Finally, we present a high-resolution transcriptome map of transient zones in the embryonic mouse forebrain.
描述指定大脑皮层发育和进化的遗传程序是神经科学的一个核心挑战。短暂的胚胎脑室和室下区中的干细胞产生迁移穿过中间区到达上覆皮质板的神经元,在那里它们分化并形成新皮质。很明显,不是一个而是多种分子途径对于通过每个细胞里程碑是必要的,然而,潜在的转录程序仍然未知。在这里,我们在显微镜下分离的细胞群体上应用差异转录组分析,以定义代表每个短暂胚胎区和这些区之间的进展的五个转录程序。这五个转录程序除了维持干细胞、神经发生、迁移和分化所需的转录本外,还包含了大量尚未被描述的基因。此外,我们发现了具有转录活性的基因间区域,这些区域可能编码独特的区特异性转录本。最后,我们展示了胚胎小鼠前脑短暂区的高分辨率转录组图谱。