Instituto Gulbenkian de Ciência, Oeiras, Portugal.
Cell Cycle. 2011 Dec 1;10(23):4026-31. doi: 10.4161/cc.10.23.18578.
In the developing vertebrate nervous system, bHLH proneural factors such as Ascl1 are known to play important regulatory roles at different stages of the neurogenic differentiation process. In spite of the wealth of information gathered on the cellular functions of proneural factors, little was known of the molecular basis for their activities, and in particular of the identity of their target genes. The development of genomic approaches is making possible the characterization of transcriptional programs at an unprecedented scale. Recently, we have used a combination of genomic location analysis by ChIP-on-chip and expression profiling in order to characterize the proneural transcription program regulated by Ascl1 in the ventral telencephalon of the mouse embryonic brain. Our results demonstrate that Ascl1 directly controls successive steps of neurogenesis and provide a molecular frame for previously described Ascl1 functions. In addition, we uncovered an important but previously unrecognized role for Ascl1 in promoting the proliferation of neural progenitors. Here we discuss our recent findings and review them in light of efforts from other laboratories to characterize the transcriptional programs downstream various proneural factors.
在脊椎动物神经系统的发育过程中，bHLH 类神经前体细胞因子（如 Ascl1）被认为在神经发生分化过程的不同阶段发挥着重要的调控作用。尽管已经收集了大量关于神经前体细胞因子的细胞功能信息，但它们的作用机制，特别是其靶基因的身份，仍然知之甚少。基因组学方法的发展使得在前所未有的规模上对转录程序进行特征描述成为可能。最近，我们结合了 ChIP-on-chip 的基因组定位分析和胚胎脑腹侧端脑的表达谱分析，以描述 Ascl1 调控的神经前体细胞转录程序。我们的结果表明，Ascl1 直接控制神经发生的连续步骤，并为先前描述的 Ascl1 功能提供了分子框架。此外，我们还揭示了 Ascl1 促进神经祖细胞增殖的一个重要但以前未被认识到的作用。在这里，我们将讨论我们最近的发现，并结合其他实验室的努力，对各种神经前体细胞因子下游的转录程序进行特征描述。
