Nuclear Dishevelled: An enigmatic role in governing cell fate and Wnt signaling.

The Dishevelled gene was first identified in Drosophila mutants with disoriented hair and bristle polarity and subsequent work has now demonstrated its importance in critical and diverse aspects of biology. Since those early discoveries, Dishevelled has been shown to coordinate a plethora of developmental and cellular processes that range from controlling cell polarity during gastrulation to partnering with chromatin modifying enzymes to regulate histone methylation at genomic loci. While the role of DVL in development is well-respected and the cytosolic function of DVL has been studied more extensively, its nuclear role continues to remain murky. In this review we highlight some of the seminal discoveries that have contributed to the field, but the primary focus is to discuss recent advances with respect to the nuclear role of Dishevelled. This nuclear function of Dishevelled is a dimension which is proving to be increasingly important yet remains enigmatic. • Novel mechanisms of Dishevelled regulation provide insight into pathologies associated with its mutation or dysfunction. • Dishevelled can be shuttled between the cytoplasm and nucleus. • Nuclear Dishevelled plays an important role in regulating genes linked with canonical Wnt/β-catenin signaling. • Key post-translationally modified Dishevelled lysines regulate its nuclear translocation and nuclear function. • Nuclear Dishevelled interacts with epigenetic enzymes at transcription regulatory regions to influence gene expression. [ABSTRACT FROM AUTHOR]