Vasconcelos Francisca F, Castro Diogo S
Molecular Neurobiology, Instituto Gulbenkian de Ciência Oeiras, Portugal.
Front Cell Neurosci. 2014 Dec 2;8:412. doi: 10.3389/fncel.2014.00412. eCollection 2014.
Proneural transcription factors (TFs) such as Ascl1 function as master regulators of neurogenesis in vertebrates, being both necessary and sufficient for the activation of a full program of neuronal differentiation. Novel insights into the dynamics of Ascl1 expression at the cellular level, combined with the progressive characterization of its transcriptional program, have expanded the classical view of Ascl1 as a differentiation factor in neurogenesis. These advances resulted in a new model, whereby Ascl1 promotes sequentially the proliferation and differentiation of neural/stem progenitor cells. The multiple activities of Ascl1 are associated with the activation of distinct direct targets at progressive stages along the neuronal lineage. How this temporal pattern is established is poorly understood. Two modes of Ascl1 expression recently described (oscillatory vs. sustained) are likely to be of importance, together with additional mechanistic determinants such as the chromatin landscape and other transcriptional pathways. Here we revise these latest findings, and discuss their implications to the gene regulatory functions of Ascl1 during neurogenesis.
原神经转录因子（TFs），如Ascl1，在脊椎动物神经发生过程中起着主要调节因子的作用，对于激活完整的神经元分化程序既是必要的也是充分的。在细胞水平上对Ascl1表达动态的新见解，结合其转录程序的逐步表征，扩展了Ascl1作为神经发生中分化因子的经典观点。这些进展产生了一个新模型，即Ascl1依次促进神经/干细胞祖细胞的增殖和分化。Ascl1的多种活性与沿着神经元谱系的不同阶段激活不同的直接靶标有关。这种时间模式是如何建立的，目前还知之甚少。最近描述的Ascl1表达的两种模式（振荡与持续）可能很重要，同时还有其他机制决定因素，如染色质景观和其他转录途径。在这里，我们回顾这些最新发现，并讨论它们对神经发生过程中Ascl1基因调控功能的影响。
