The exon junction complex regulates the splicing of cell polarity gene DLG1 to control Wingless signaling in development

Animal development involves different signaling pathways that coordinate complex behaviors of the cells, such as changes in cell number or cell shape. One such pathway involves a protein called Wingless/Wnt, which controls cell fate and growth and is also involved in tumor formation in humans. In recent decades, scientists have made a lot of progress in understanding how this signaling pathway operates. However, it is not well understood how the Wingless/Wnt signaling pathway interacts with other regulatory networks during development. Now, Liu, Li et al. unveil a new regulatory network that controls the Wingless/Wnt pathway in fruit flies and in mammalian cells grown in the laboratory. The experiments show that an RNA binding protein family named the Exon Junction Complex positively regulates a protein called Dishevelled, which serves as a hub in the Wingless/Wnt pathway. The Exon Junction Complex keeps the amount of Dishevelled protein in check via an interaction with another protein referred to as Discs large. Further experiments indicated that Discs large binds to and protects Dishevelled from being degraded inside the cell. Liu et al.'s findings highlight a new control mechanism for the Wingless/Wnt signaling pathway. In the future, the findings may also aid the development of new approaches to prevent or treat birth defects and cancer.