Verheyen E M, Purcell K J, Fortini M E, Artavanis-Tsakonas S
Howard Hughes Medical Institute, Yale University, New Haven, Connecticut 06536, USA.
Genetics. 1996 Nov;144(3):1127-41. doi: 10.1093/genetics/144.3.1127.
The Notch receptor controls cell fate decisions throughout Drosophila development. Truncated, ligand-independent forms of this protein delay or block differentiation. We have previously shown that expression of the intracellular domain of the receptor under the control of the sevenless enhancer/promoter induces a rough eye phenotype in the adult fly. Analysis of the resultant cellular transformations suggested that this form of Notch acts as a constitutively activated receptor. To identify gene products that interact with Notch, a second-site mutagenesis screen was performed to isolate enhancers and suppressors of the eye phenotype caused by expression of these activated Notch molecules. We screened 137,000 mutagenized flies and recovered 290 dominant modifiers. Many new alleles of previously identified genes were isolated, as were mutations defining novel loci that may function in the Notch signaling pathway. We discuss the data with respect to known features of Notch receptor signaling and Drosophila eye development.
Notch受体在果蝇的整个发育过程中控制细胞命运的决定。这种蛋白质的截短的、不依赖配体的形式会延迟或阻断分化。我们之前已经表明，在无七受体增强子/启动子的控制下，受体细胞内结构域的表达会在成年果蝇中诱导出粗糙眼表型。对由此产生的细胞转化的分析表明，这种形式的Notch作为一种组成型激活受体发挥作用。为了鉴定与Notch相互作用的基因产物，进行了二次位点诱变筛选，以分离由这些激活的Notch分子表达引起的眼表型的增强子和抑制子。我们筛选了137,000只诱变果蝇，获得了290个显性修饰因子。分离出了许多先前鉴定基因的新等位基因，以及定义了可能在Notch信号通路中起作用的新位点的突变。我们根据Notch受体信号传导和果蝇眼睛发育的已知特征来讨论这些数据。
