Arias Ronald A, 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, USA.
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, USA.
Dev Biol. 2025 Mar;519:21-29. doi: 10.1016/j.ydbio.2024.12.001. Epub 2024 Dec 7.
The process by which the Drosophila R7 photoreceptor is specified has become a classic model for understanding how cell-cell signals direct cell fates. In the R7 precursor cell, both the Notch and receptor tyrosine kinase (RTK) signaling pathways are active, and the information they encode directs the specification of the R7 photoreceptor identity. In this process, Notch performs three distinct functions: it both opposes and promotes the actions of the RTK pathway to specify the photoreceptor fate, and it determines the type of photoreceptor that is specified. The RTK pathway drives transcription of phyl - a gene expression necessary for photoreceptor specification. We show that Notch activity induces transcription of the yan gene which encodes a transcriptional repressor of phyl. This defines an antagonism between the two pathways, with RTK promoting and Notch opposing phyl transcription. We previously showed that Notch activity supplies Sevenless to the R7 precursor to allow the RTK pathway hyperactivation required to overcome the Notch repression, and we now identify the regulation of Yan activity as a site of integration of RTK and Notch signaling pathways. Once the cell is specified as a photoreceptor, the third Notch function then prevents seven-up (svp) transcription. The Svp transcription factor directs the R1/6 photoreceptor fate, and the prevention of its expression ensures the default R7 specification.
果蝇R7光感受器的特化过程已成为理解细胞间信号如何指导细胞命运的经典模型。在R7前体细胞中，Notch信号通路和受体酪氨酸激酶（RTK）信号通路均处于激活状态，它们编码的信息指导R7光感受器身份的特化。在此过程中，Notch发挥三种不同的功能：它既对抗又促进RTK通路的作用以特化光感受器命运，并且它决定特化的光感受器类型。RTK通路驱动光感受器特化所需的phyl - a基因表达的转录。我们发现Notch活性诱导yan基因的转录，该基因编码phyl的转录抑制因子。这定义了两条通路之间的拮抗作用，RTK促进而Notch抑制phyl转录。我们之前表明Notch活性向R7前体细胞提供Sevenless，以允许RTK通路过度激活以克服Notch抑制，并且我们现在确定Yan活性的调节是RTK和Notch信号通路整合的位点。一旦细胞被特化为光感受器，Notch的第三种功能随后会阻止seven-up（svp）转录。Svp转录因子指导R1/6光感受器命运，阻止其表达可确保默认的R7特化。
