锯齿状和 Nerfin-1 转录因子协同作用维持神经元细胞命运。

The Scalloped and Nerfin-1 Transcription Factors Cooperate to Maintain Neuronal Cell Fate.

机构信息

Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3010, Australia.

Bioinformatic Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3053, Australia; School of Computing and Information Systems, University of Melbourne, Parkville, VIC 3010, Australia.

出版信息

Cell Rep. 2018 Nov 6;25(6):1561-1576.e7. doi: 10.1016/j.celrep.2018.10.038.

DOI:10.1016/j.celrep.2018.10.038

PMID:30404010

Abstract

The ability of cells to stably maintain their fate is governed by specific transcription regulators. Here, we show that the Scalloped (Sd) and Nervous fingers-1 (Nerfin-1) transcription factors physically and functionally interact to maintain medulla neuron fate in the Drosophila melanogaster CNS. Using Targeted DamID, we find that Sd and Nerfin-1 occupy a highly overlapping set of target genes, including regulators of neural stem cell and neuron fate, and signaling pathways that regulate CNS development such as Notch and Hippo. Modulation of either Sd or Nerfin-1 activity causes medulla neurons to dedifferentiate to a stem cell-like state, and this is mediated at least in part by Notch pathway deregulation. Intriguingly, orthologs of Sd and Nerfin-1 have also been implicated in control of neuronal cell fate decisions in both worms and mammals. Our data indicate that this transcription factor pair exhibits remarkable biochemical and functional conservation across metazoans.

摘要

细胞稳定维持其命运的能力受特定转录调控因子的控制。在这里，我们表明 Scalloped（Sd）和 Nervous fingers-1（Nerfin-1）转录因子在物理和功能上相互作用，以维持果蝇中枢神经系统中的 Medulla 神经元命运。使用靶向 DamID，我们发现 Sd 和 Nerfin-1 占据了高度重叠的一组靶基因，包括神经干细胞和神经元命运的调节剂，以及调节 CNS 发育的信号通路，如 Notch 和 Hippo。调节 Sd 或 Nerfin-1 的活性会导致 Medulla 神经元去分化为类似干细胞的状态，这至少部分是通过 Notch 途径的失调来介导的。有趣的是，Sd 和 Nerfin-1 的同源物也被牵连到线虫和哺乳动物中神经元细胞命运决定的控制中。我们的数据表明，这个转录因子对在后生动物中表现出显著的生化和功能保守性。