Dishevelled: In Vivo Roles of a Multifunctional Gene Family During Development - Current Topics in Developmental Biology - page 215

perpendicular to the apical-basal (AB) axis of the cell. Manifestations of this
polarity include uniformly oriented trichomes on the wing epithelial cells
and bristles on the thorax, abdomen, and leg and precisely coordinated
orientation of ommatidial units of the compound eye.
Studies over the past few years have identified a large number of novel
cytoplasmic or membrane proteins, including a “core” PCP group con-
sisting of Flamingo, Diego, Prickle, and Strabismus/Van Gogh, in addition
to Frizzled and Dishevelled. In Xenopus and zebrafish, almost all the homo-
logues of the fly “core” PCP proteins have been found to control conver-
gent extension, a coordinated extension of the A-P axis with concomitant
narrowing of the medial-lateral axis ( Carreira-Barbosa et al., 2003; Darken
et al., 2002; Goto & Keller, 2002 ; Kinoshita, Iioka, Miyakoshi, & Ueno,
2003; Park & Moon, 2002; Takeuchi et al., 2003 ; Veeman, Slusarski,
Kaykas, Louie, & Moon, 2003; Wallingford, Fraser, & Harland, 2002;
Wallingford et al., 2000 ). In contrast to the PCP pathway in fly, both
Wnt5a and Wnt11 have been implicated in regulating convergent extension
in vertebrates ( Heisenberg et al., 2000 ; Yamanaka et al., 2002). During
convergent extension, several PCP proteins have been shown to control the
polarity of lamellipodial protrusions that drive polarized cell intercalation
( Jessen et al., 2002; Wallingford et al., 2000 ). In zebrafish, the PCP pathway
appears to regulate convergent extension, in part, through determining the
orientation of cell division ( Gong, Mo, & Fraser, 2004 ).
3. CONSERVED MAMMALIAN PCP PATHWAY
Mouse genetics has provided compelling evidence that a homologous
PCP pathway also exists in mammals to regulate a diverse array of morpho-
genetic processes.
3.1. PCP pathway in inner ear development
In Loop-tail ( Lp ) mutant mice, which harbor a loss-of-function point muta-
tion in Vangl2 , one of the mammalian homologues of the fly PCP gene
Strabismus/Van Gogh ( Stbm/Vang ), the uniform orientation of stereocilia
on the sensory hairs cells of the cochlea is disrupted ( Kibar et al., 2001;
Montcouquiol et al., 2003; Murdoch, Doudney, Paternotte, Copp, &
Stanier, 2001 ). Orientation of these stereocilia, reminiscent of the
trichome on epithelial cells of the fly wing, is a likely manifestation of
PCP in mammals ( Lewis & Davies, 2002 ). In addition to Lp , mutations
of several other PCP homologues in the mouse result in misorientation