IMBA - Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna Biocenter (VBC), Vienna, Austria.
Elife. 2019 Jul 22;8:e46566. doi: 10.7554/eLife.46566.
Neural progenitors undergo temporal patterning to generate diverse neurons in a chronological order. This process is well-studied in the developing brain and conserved in mammals. During larval stages, intermediate neural progenitors (INPs) serially express Dichaete (D), grainyhead (Grh) and eyeless (Ey/Pax6), but how the transitions are regulated is not precisely understood. Here, we developed a method to isolate transcriptomes of INPs in their distinct temporal states to identify a complete set of temporal patterning factors. Our analysis identifies odd-paired (opa), as a key regulator of temporal patterning. Temporal patterning is initiated when the SWI/SNF complex component Osa induces D and its repressor Opa at the same time but with distinct kinetics. Then, high Opa levels repress D to allow Grh transcription and progress to the next temporal state. We propose that Osa and its target genes opa and D form an incoherent feedforward loop (FFL) and a new mechanism allowing the successive expression of temporal identities.
神经祖细胞经历时间模式化,以按时间顺序生成多种神经元。这个过程在发育中的大脑中得到了很好的研究,并在哺乳动物中得到了保守。在幼虫阶段,中间神经祖细胞(INPs)依次表达 Dichaete(D)、grainyhead(Grh)和 eyeless(Ey/Pax6),但过渡是如何调节的尚不清楚。在这里,我们开发了一种方法来分离处于不同时间状态的 INPs 的转录组,以鉴定一整套时间模式化因子。我们的分析确定了 odd-paired(opa)是时间模式化的关键调节因子。当 SWI/SNF 复合物成分 Osa 同时但具有不同动力学诱导 D 和其抑制剂 Opa 时,时间模式化就开始了。然后,高 Opa 水平抑制 D,允许 Grh 转录并进入下一个时间状态。我们提出,Osa 及其靶基因 opa 和 D 形成一个非相干前馈环(FFL)和一种允许时间身份连续表达的新机制。