Department of Cell Biology, NYU Grossman School of Medicine, New York, NY, USA.
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.
Nat Commun. 2024 Aug 17;15(1):7091. doi: 10.1038/s41467-024-51429-z.
The integration of extrinsic signaling with cell-intrinsic transcription factors can direct progenitor cells to differentiate into distinct cell fates. In the developing Drosophila eye, differentiation of photoreceptors R1-R7 requires EGFR signaling mediated by the transcription factor Pointed, and our single-cell RNA-Seq analysis shows that the same photoreceptors require the eye-specific transcription factor Glass. We find that ectopic expression of Glass and activation of EGFR signaling synergistically induce neuronal gene expression in the wing disc in a Pointed-dependent manner. Targeted DamID reveals that Glass and Pointed share many binding sites in the genome of developing photoreceptors. Comparison with transcriptomic data shows that Pointed and Glass induce photoreceptor differentiation through intermediate transcription factors, including the redundant homologs Scratch and Scrape, as well as directly activating neuronal effector genes. Our data reveal synergistic activation of a multi-layered transcriptional network as the mechanism by which EGFR signaling induces neuronal identity in Glass-expressing cells.
外在信号与细胞内转录因子的整合可以指导祖细胞分化为不同的细胞命运。在发育中的果蝇眼中，光感受器 R1-R7 的分化需要转录因子 Pointed 介导的 EGFR 信号，我们的单细胞 RNA-Seq 分析表明，相同的光感受器需要眼睛特异性转录因子 Glass。我们发现 Glass 的异位表达和 EGFR 信号的激活以 Pointed 依赖的方式协同诱导 wing disc 中的神经元基因表达。靶向 DamID 揭示了 Glass 和 Pointed 在发育中的光感受器的基因组中有许多共同的结合位点。与转录组数据的比较表明，Pointed 和 Glass 通过中间转录因子诱导光感受器分化，包括冗余同源物 Scratch 和 Scrape，以及直接激活神经元效应基因。我们的数据揭示了一个多层次转录网络的协同激活，作为 EGFR 信号在表达 Glass 的细胞中诱导神经元特性的机制。
