Stratmann Johannes, Gabilondo Hugo, Benito-Sipos Jonathan, Thor Stefan
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Departamento de Biología, Universidad Autónoma de Madrid, Madrid, Spain.
Elife. 2016 Oct 14;5:e19311. doi: 10.7554/eLife.19311.
During embryonic nervous system development, neuroblasts express a programmed cascade of five temporal transcription factors that govern the identity of cells generated at different time-points. However, these five temporal genes fall short of accounting for the many distinct cell types generated in large lineages. Here, we find that the late temporal gene sub-divides its large window in neuroblast 5-6 by simultaneously activating two cell fate determination cascades and a sub-temporal regulatory program. The sub-temporal program acts both upon itself and upon the determination cascades to diversify the window. Surprisingly, the early temporal gene acts as one of the sub-temporal genes within the late window. Intriguingly, while the temporal gene activates the two determination cascades and the sub-temporal program, spatial cues controlling cell fate in the latter part of the 5-6 lineage exclusively act upon the determination cascades.
在胚胎神经系统发育过程中,神经母细胞表达一系列由五个时间转录因子组成的程序性级联,这些转录因子决定了在不同时间点产生的细胞的特性。然而,这五个时间基因不足以解释在大型谱系中产生的许多不同细胞类型。在这里,我们发现晚期时间基因通过同时激活两个细胞命运决定级联和一个亚时间调节程序,在神经母细胞5-6中细分其大窗口。亚时间程序作用于自身和决定级联,以使窗口多样化。令人惊讶的是,早期时间基因在晚期窗口内作为亚时间基因之一发挥作用。有趣的是,虽然时间基因激活了两个决定级联和亚时间程序,但控制5-6谱系后半部分细胞命运的空间线索仅作用于决定级联。