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细胞系中视网膜决定基因网络新组分的鉴定

Identification of novel components of the retinal determination gene network in cell lines.

作者信息

Drewell Robert A, Dresch Jacqueline M

机构信息

Department of Biology, Clark University, Worcester, MA, USA.

出版信息

Open Biol. 2025 Jul;15(7):250012. doi: 10.1098/rsob.250012. Epub 2025 Jul 16.

Abstract

The retinal determination genetic network controls the development of the visual system in all seeing animals through the molecular regulation of cells to adopt an eye tissue fate. The compound eye of the fruit fly, , is an excellent model system to study the complex mechanisms within the network that regulate specification of cellular identity during embryogenesis. In , the two paralogues, and , sit at the very pinnacle of the network and their expression early in development activates critical downstream components of the retinal determination pathway. In this study, we investigate the expression of 21 known components of the network in two established embryonic cell lines, Kc167 and S2 cells, that show reciprocal expression patterns for the two paralogues. Network mapping reveals that many of the components of the network demonstrate extensive interactions with additional factors. Integrating the transcriptional profile of the cell lines, interaction maps and embryonic expression patterns enables us to identify 16 potential novel components of the genetic network, 11 of which are transcription factors. We confirm the regulatory potential for a subset of the novel transcription factors through the identification of predicted binding sites in previously characterized enhancers for the core genes in the network.

摘要

视网膜决定基因网络通过对细胞的分子调控使其采用眼组织命运,从而控制所有视觉动物视觉系统的发育。果蝇的复眼是研究该网络中调节胚胎发育过程中细胞身份特化的复杂机制的优秀模型系统。在果蝇中,两个旁系同源物,即 和 ,处于该网络的顶端,它们在发育早期的表达激活了视网膜决定途径的关键下游成分。在本研究中,我们调查了网络中21个已知成分在两种已建立的胚胎细胞系Kc167和S2细胞中的表达,这两种细胞系对两个旁系同源物呈现相反的表达模式。网络图谱显示,该网络的许多成分与其他因子存在广泛的相互作用。整合细胞系的转录谱、相互作用图谱和胚胎表达模式,使我们能够识别出该基因网络的16个潜在新成分,其中11个是转录因子。我们通过在先前表征的网络核心基因增强子中识别预测的结合位点,证实了一部分新转录因子的调控潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c81f/12303109/c6d8570e82e9/rsob.250012.fg002.jpg

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