Dishevelled: A masterful conductor of complex Wnt signals

The Dishevelled gene was first identified in Drosophila mutants with disoriented hair and bristle polarity [1–3]. The Dsh gene (Dsh/Dvl, in Drosophila and vertebrates respectively) gained popularity when it was discovered that it plays a key role in segment polarity during early embryonic development in Drosophila [4]. Subsequently, the vertebrate homolog of Dishevelled genes were identified in Xenopus (Xdsh), mice (Dvl1, Dvl2, Dvl3), and in humans (DVL1, DVL2, DVL3) [5–10]. Dishevelled functions as a principal component of Wnt signaling pathway and governs several cellular processes including cell proliferation, survival, migration, differentiation, polarity and stem cell renewal. This review will revisit seminal discoveries and also summarize recent advances in characterizing the role of Dishevelled in both normal and pathophysiological settings. •Dishevelled (DVL) proteins function as principal components of Wnt signaling pathway and govern several cellular processes.•DVL integrates and relays complex Wnt signals, yet how it conducts this symphony of activity still remains poorly understood.•This review discusses the function of DVL in the Wnt signaling pathway in normal and aberrant cellular contexts.•Additionally, it highlights novel roles within the nucleus and discusses new binding partners and novel mechanisms of post-translational regulation.