Wingless signaling: A genetic journey from morphogenesis to metastasis

Abstract

This FlyBook chapter summarizes the history and the current state of our understanding of the Wingless signaling pathway. Wingless, the fly homolog of the mammalian Wnt oncoproteins, plays a central role in pattern generation during development. Much of what we know about the pathway was learned from genetic and molecular experiments in Drosophila melanogaster, and the core pathway works the same way in vertebrates. Like most growth factor pathways, extracellular Wingless/ Wnt binds to a cell surface complex to transduce signal across the plasma membrane, triggering a series of intracellular events that lead to transcriptional changes in the nucleus. Unlike most growth factor pathways, the intracellular events regulate the protein stability of a key effector molecule, in this case Armadillo/β-catenin. A number of mysteries remain about how the “destruction complex” destabilizes β-catenin and how this process is inactivated by the ligand-bound receptor complex, so this review of the field can only serve as a snapshot of the work in progress.