Dishevelled: In Vivo Roles of a Multifunctional Gene Family During Development - Current Topics in Developmental Biology - page 224

12. DVL2/3 DOUBLE MUTANTS
Dvl2 þ / ; Dvl3 / double mutants at E18.5 appear shorter along the
A-P axis and show an abnormal head shape, forebrain defects, and a trun-
cated snout, as well as a shortened and kinked tail. Craniorachischisis was
observed in two Dvl2 þ / ; Dvl3 / mutants, and one of these also showed
other severe phenotypes, including gastroschisis and absence of the tail.
Dvl2 / ; Dvl3 þ / mutants display craniorachischisis, pericardial effusion,
and abnormal looping of the heart, as well as severe posterior truncation,
and do not survive beyond E9.5 ( Etheridge et al., 2008 ). No Dv2 / ;
Dvl3 / embryos have been recovered from litters collected from E8.5 on-
ward, due to severe gastrulation defects and lethality earlier in development
(see below). These findings are consistent with the interpretation that there
is functional overlap among the Dvl genes.
13. DVL1,2,3 TRIPLE MUTANTS DISPLAY DEFECTS IN THE
POSTERIOR PLACEMENT OF NODAL CILIA (FIG. 9.1)
As noted for the Dvl double mutants, the phenotypes of Dvl1/2/3 triple
mutants further demonstrated that there is substantial overlapping and redun-
dant functions among the three Dvl genes. In collaboration with Hiroshi
Hamada (Osaka University), we found that the three Dvl genes participate
in the planar polarization of node cells to determine the rotational axis of nodal
cilia ( Hashimoto et al., 2010 ). Rotational movement of the node cilia generates
a leftward fluid flow in themouse embryo because the cilia are posteriorly tilted
( Nonaka et al., 2005; Okada, Takeda, Tanaka, Belmonte, &Hirokawa, 2005 ),
but it was not known how A-P information is translated into the posterior tilt
of the node cilia. We found that the basal body of node cilia is initially
positioned centrally but then gradually shifts toward the posterior side of the
node cells, a shift that was impaired along with malpositioning of the basal
body and unidirectional nodal flow in compound mutant mice lacking Dvl
genes. The basal body was normally positioned in the node cells of
Wnt3a / embryos (coding for a canonical Wnt involved in gastrulation
movements), but inhibition of Rac1, a component of the noncanonical
Wnt signaling pathway, impaired the polarized localization of the basal
body in wild-type embryos. Dvl2-EGFP and Dvl3-EYFP proteins were
localized to the apical side of the node cells, and their location was polarized