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cortical region (Darras et al. 1997 ; Marikawa et al. 1997 ; Marikawa and Elinson
1999 ). By correlating its activity with various axis-inducing molecules, this vegetal
cortical cytoplasm was found to mimic intracellular activation of the Wnt/beta-
catenin signaling pathway (Marikawa and Elinson 1999 ). Curiously, UV-irradiation
experiments in Xenopus oocytes indicated that this cytoplasm showed cell cycle-
dependent sensitivity to UV Irradiation of the egg disrupts microtubule assembly
and cortical rotation, although the activity of the vegetal cortical cytoplasm itself is
not affected. By contrast, UV-irradiation of full-grown oocytes effectively does
eliminate the dorsalizing ability of vegetal cytoplasm and ventralizes embryos
(Holwill et al. 1987 ; Elinson and Pasceri 1989 ). Eggs irradiated as oocytes undergo
normal cortical rotation and are not rescued by tipping (Elinson and Pasceri 1989 ),
suggesting that a critical component of axis induction is absent.
The target of UV irradiation in the oocyte is not known, but either its action is
completed by oocyte maturation or it is subsequently sequestered and no longer
susceptible to irradiation. These features may be useful in identifying potential can-
didate molecules. In apparent support of a direct cytoplasmic beta-catenin activation
model, particles of exogenous Wnt-activating proteins, Dvl2-GFP (Miller et al.
1999 ) and Frat1-GFP (Weaver et al. 2003 ) were shown to undergo dorsal translocation
during cortical rotation, suggesting that the dorsalizing activity might be composed
of beta-catenin stabilizing agents. These molecules might then directly stabilize
beta-catenin, or act by sensitizing dorsal cells to Wnt signals. Further indications of
potential Wnt ligand-independent dorsalizing mechanisms came from observations
that overexpression of secreted Wnt antagonists were unable to suppress endoge-
nous axis formation (Hoppler et al. 1996 ; Leyns et al. 1997 ; Wang et al. 1997 ).
More recent studies in Xenopus suggest a more typical Wnt signaling model,
with maternal Wnt11b acting to induce beta-catenin activity. Maternal wnt11b is
localized to the vegetal cortex during oogenesis via a mitochondrial cloud- dependent
pathway (see Chap. 8 ) and was initially considered a prime candidate for the vegetal
dorsally activity, based on its activity in UV-rescue experiments. In light of the evi-
dence favoring the direct activation model (see above), and other experiments show-
ing that Wnt11b can regulate beta-catenin-independent signaling, a role for wnt11b
in axis formation was later discounted. However, a reinvestigation using antisense
oligo mediated maternal mRNA depletion showed that maternal wnt11b is indeed
required for axis formation (Tao et al. 2005 ).
Wnt11b is though to act in concert with uniformly expressed Wnt5a (Cha et al.
2008 ), forming extracellular complexes with each other and with other proteins,
including heparin sulfate proteoglycans and the Nodal coreceptor Tdgf1 (Tao et al.
2005 ; Cha et al. 2008 , 2009 ). The activity of this Wnt complex can be antagonized
by maternal Dkk1, suggesting a model in which cortical rotation tips the balance of
Wnt activity to overcome generalized Wnt antagonism (Cha et al. 2008 ). The mech-
anism of Wnt11b enrichment dorsally following cortical rotation is unclear, as both
enrichment of total wnt11b RNA (Tao et al. 2005 ) or enhanced polyadenylation
(Schroeder et al. 1999 ) have been proposed. A similar mechanism, albeit with dif-
ferent Wnts and antagonists, has been proposed in zebrafish (see below). However,
Wnt11b can also regulate beta-catenin levels in an autocrine fashion in fully grown
D.W. Houston