Control of Cell Polarity and Asymmetric Division in C. elegans - Current Topics in Developmental Biology - page 54

1. CORTICAL ASYMMETRY OF Wnt SIGNALING
COMPONENTS
The mechanism of Wnt/ b -catenin asymmetry pathway has been
mostly studied in some specific cells: embryonic EMS blastomere, larval
T cell, and somatic gonadal precursors (SGPs) ( Mizumoto & Sawa,
2007b ). These cells as well as most other mitotic cells in Caenorhabditis elegans
divide along the anterior-posterior axis. Asymmetric division of EMS pro-
duces anterior MS and posterior E daughters that generate mesoderm and
endoderm, respectively, while the postembryonic T cell divides asymmet-
rically to produce anterior hypodermal and posterior neural precursors.
Among them, the T cell as well as seam cells (see below) are hypodermal
cells and divide along planer rather than apical-basal orientation. Therefore,
their polarity can be considered as planer polarity. In fact, similar to the
PCP pathway, Frizzled receptors LIN-17 and MOM-5 are localized to
the posterior cell cortex in the T cell and embryonic cells, respectively
( Goldstein, Takeshita, Mizumoto, & Sawa, 2006; Park, Tenlen, &
Priess, 2004 )( Fig. 3.1 ). Similarly, Dishevelled proteins DSH-2 and
MIG-5 (collectively called DSHs) are localized to the posterior cortex
in the T, seam, and EMS cells ( Mizumoto & Sawa, 2007a ).
However, involvements of the other core PCP components, such as
homologues of Van Gogh, Prickle, and Flamingo in the asymmetric
divisions have not been clearly demonstrated. Further, components
of the canonical Wnt pathway, WRM-1/ b -catenin, APR-1/APC,
and PRY-1/Axin are involved in the pathway and localized to the
anterior cell cortex, opposite sides of the DSH localization ( Fig. 3.1 B
and C) ( Mizumoto & Sawa, 2007a; Nakamura et al., 2005; Sugioka,
Mizumoto, & Sawa, 2011; Takeshita & Sawa, 2005 ). Therefore, in
terms of signaling components, the Wnt/ b -catenin asymmetry
pathway is similar to the canonical Wnt pathway, even though
the asymmetric localization reminds us of the PCP regulation. These
asymmetric localizations are regulated by Wnt and Frizzled proteins.
However, detailed molecular mechanisms remain elusive. Unlike
b -catenin of other species, WRM-1 does not have GSK3 b
phosphorylation sites and does not bind to HMR-1/cadherin
( Korswagen, Herman, & Clevers, 2000; Natarajan, Witwer, &
Eisenmann, 2001 ). Therefore, it is still a mystery how WRM-1
localizes to the cortex and how it is regulated by Wnts.