Dishevelled: In Vivo Roles of a Multifunctional Gene Family During Development - Current Topics in Developmental Biology - page 218

mpk1 genetically interacts with another core PCP gene Vangl2/stbm in epi-
blast formation, suggesting that PCP components are commonly required
for the establishment and/or the maintenance of epiblast AB polarity. Thus,
mpk1 appears to play an important role in AB epiblast polarity formation as
part of the PCP pathway.

4. DVL GENES: CROSSROADS OF WNT AND PCP
PATHWAYS
As noted above, Fz and Dishevelled from Drosophila melanogaster partic-
ipate in Wnt/Wg signaling and the PCP pathway. The PCP pathway in
Drosophila and convergent extension in vertebrates are regulated by the same
genetic pathway (reviewed in Wang & Nathans, 2007; Zallen, 2007 ). In
Drosophila and Xenopus ( Axelrod, Miller, Shulman, Moon, & Perrimon,
1998; Wallingford et al., 2000 ), it is known that distinct domains of Dvl
proteins (DIX, DEP, and PDZ domains) are important for distinguishing
between Wnt/Wg and PCP signaling. The DIX domain is mainly
involved in the Wnt pathway: deletion of the DIX ( DIX) domain

abolishes Wnt activity, but PCP activity is maintained. In contrast,
deletion of the PDZ or C-terminal part of the DEP domain (

D

D PDZ and

D

DEP, respectively) affects only the PCP but not the Wnt pathway in
Drosophila . Thus, in vivo analysis of Dvl proteins can be used to define the
pathways mediated by Dvls to produce phenotypic effects, including in
mice. We have shown that similar mutational analysis can define Dvl
functions in vivo in mammals (see below).

5. SINGLE MUTANTS FOR DVL GENES IN THE MOUSE:
UNIQUE PHENOTYPES (FIG. 9.1)
We have been studying the Dvl family of genes in mice to gain insights
into Dvl function and to investigate the function of canonical Wnt and non-
canonical PCP pathways in vivo . The three murine Dishevelled genes, Dvl1 ,
Dvl2 , and Dvl3 , are all widely expressed in embryonic and adult tissues,
suggesting that there may be functional overlap. To test this, we have made
mouse knock-outs for each of the Dvl genes by conventional gene targeting.
Surprisingly, analysis of these single mutants uncovered unique phenotypes
for each of the Dvl genes.