Abstract
Dishevelled (DVL) proteins are highly conserved in the animal kingdom and are important key players in β-Catenin-dependent and -independent Wnt signaling pathways. Vertebrate genomes typically comprise three DVL genes, DVL1, DVL2, and DVL3. Expression patterns and developmental functions of the three vertebrate DVL proteins however, are only partially redundant in any given species. Moreover, expression and function of DVL isoforms have diverged between different vertebrate species. All DVL proteins share basic functionality in Wnt signal transduction. Additional, paralog-specific interactions and functions combined with context-dependent availability of DVL isoforms may play a central role in defining Wnt signaling specificity and add selectivity toward distinct downstream pathways. In this review, we recapitulate briefly cellular functions of DVL paralogs, their role in vertebrate embryonic development and congenital disease.
Highlights
The Dishevelled phenotype has been described the first time in Drosophila close to 60 years ago (Fahmy and Fahmy, 1959) and the diverse molecular functions of Dishevelled (DVL) proteins still stimulate intensive research
Evidence is accumulating that Wnt pathways should be considered as a signaling network, individual pathways have been subdivided into the Wnt/βCatenin pathway and the β-Catenin–independent pathways including Wnt/planar cell polarity (PCP), Wnt/Ca2+, and Wnt/STOP signaling, all of which involve DVL
By contrast vertebrate genomes comprise genes for three DVL paralogs (DVL1-3), which have most likely arisen from two rounds of genome duplication
Summary
The Dishevelled (dsh1) phenotype has been described the first time in Drosophila close to 60 years ago (Fahmy and Fahmy, 1959) and the diverse molecular functions of Dishevelled (DVL) proteins still stimulate intensive research. To date DVL is considered the central intracellular effector of Wnt signaling pathways, which play key roles in establishing and patterning of the body axes and in the control of proliferation, differentiation, planar cell polarity (PCP), and cell movements throughout the animal kingdom. DVL and its core functions in β-Catenin-dependent and -independent Wnt pathways are highly conserved. The genomes of Drosophila and most other invertebrates harbor only a single DVL gene. By contrast vertebrate genomes comprise genes for three DVL paralogs (DVL1-3), which have most likely arisen from two rounds of genome duplication (reviewed in Kasahara, 2007; Dillman et al, 2013). The still high degree of conservation among the three vertebrate DVL paralogs raises the question to which extent they have undergone functional diversification since obviously a single protein is sufficient to mediate DVL functions in invertebrates
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