Ronald A Arias, Yannis E Mavromatakis, Tomlinson Andrew
Zuckerman Institute, Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, Jerome L. Greene Science Center, Level 9 Room 028 3227 Broadway New York, NY 10027.
bioRxiv. 2025 Jan 30:2025.01.30.635716. doi: 10.1101/2025.01.30.635716.
When a cell receives multiple developmental signals simultaneously, the intracellular transduction pathways triggered by those signals are coincidentally active. How then, do the cells decode the information contained within those multiple active pathways to derive a precise developmental directive? The specification of the Drosophila R7 photoreceptor is classic model system for investigating such questions. The R7 fate is specified by the combined actions of the of the Notch (N) and receptor tyrosine kinase (RTK) signaling pathways. The two pathways cross-communicate in an integrative mechanism but also supply information independently of each other. Collectively, this information is summed to provide an unambiguous directive for the R7 fate. Our goal is to understand these mechanisms. Here, we examine how N activity represses transcription of the gene in the process of information integration with the RTK pathway, and how it represses expression of the gene in an independent mechanism needed for R7 fate. We describe how N activity achieves these transcriptional repressions, and identify Enhancer of Split transcription factors as the mediators of those actions.
当一个细胞同时接收到多个发育信号时，由这些信号触发的细胞内转导途径会同时处于活跃状态。那么，细胞是如何解读这些多个活跃途径中包含的信息，以得出精确的发育指令呢？果蝇R7光感受器的特化是研究此类问题的经典模型系统。R7命运是由Notch（N）信号通路和受体酪氨酸激酶（RTK）信号通路的联合作用所决定的。这两条通路以一种整合机制相互交叉通讯，但也彼此独立地提供信息。总体而言，这些信息被汇总起来，为R7命运提供明确的指令。我们的目标是了解这些机制。在这里，我们研究了在与RTK通路进行信息整合的过程中，N活性如何抑制该基因的转录，以及它如何在R7命运所需的独立机制中抑制该基因的表达。我们描述了N活性是如何实现这些转录抑制的，并确定分裂增强子转录因子是这些作用的介导者。
