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et al. 1998 ; Sampath et al. 1998 ; Erter et al. 1998 ), and these abnormalities can be
rescued by YSL-specific expression of Nodal ligands. Additionally, nodal1 is
maternally expressed in zebrafish and its mRNA localized to the presumptive dorsal
side at the 4-cell stage, through an uncharacterized mechanism involving microtu-
bules (Gore et al. 2005 ). The role of this maternal transcript is not fully clear; it may
lead to enhanced Nodal activity dorsally, although there are hints that the 3′UTR
may help promote dorsal nuclear beta-catenin accumulation by acting as a noncod-
ing RNA (Lim et al. 2012 ).
In addition to stimulating higher levels of Nodal activity, dorsal beta-catenin
directly initiates a set of gene regulatory interactions that integrate with Nodal sig-
naling in the prospective mesendoderm (Fig. 6.8). In Xenopus, Wnt/beta-catenin
signaling directly activates the paired homeobox paralogues siamois1 (sia1) and
siamois2 (twin/sia2) in dorsovegetal cells in the blastula (Lemaire et al. 1995 ;
Brannon and Kimelman 1996 ; Brannon et al. 1997 ). Sia1/2 integrate with Nodal/
Tgfb signaling in activating additional genes in the anterior endoderm and organizer,
including cerberus, hhex, and goosecoid, whose promoters are bound by Sia1
(Ishibashi et al. 2008 ; Rankin et al. 2011 ; Sudou et al. 2012 ). Maternal beta-catenin
signaling is also required to repress early bmp4 expression dorsally in Xenopus
(Baker et al. 1999 ), and this is also mediated through Sia1/2. These proteins are
required to repress Bone Morphogenetic Protein (BMP) expression and activity dor-
sally, which is essential for dorsal mesoderm formation (see Sect. 6.4.1). Sia1/2 acti-
vate the expression of several BMP antagonists, including noggin (nog) and chordin
(chrd) (Ishibashi et al. 2008 ), and also indirectly repress bmp4 expression, through
an unknown intermediate. Nog and chrd expression are maintained by Nodal signal-
ing, but initial expression depends only on maternal beta-catenin (Wessely et al.
2001 ). Although Sia1/2 are predominantly expressed in mesendodermal precursors,
their expression can extend into some equatorial precursors that escape mesoderm
induction (Kuroda et al. 2004 ), where they specify early neural fate and the prospec-
tive anterior neuroectoderm (Ishibashi et al. 2008 ; Klein and Moody 2015 ).
Similarly, in zebrafish maternal beta-catenin activates expression of dharma in
dorsal marginal blastomeres and dYSL. Dharma is a paired homoebox gene some-
what functionally analogous to sia1, but unrelated by descent (Fekany et al. 1999 ;
Kelly et al. 2000 ). Dharma has numerous roles in dorsoventral patterning, including
direct repression of bmp2b (Koos and Ho 1999 ; Leung et al. 2003a). Interestingly,
both sia1 and dharma are expressed prior to major zygotic gene activation in frogs
and fish (Yang et al. 2002 ; Leung et al. 2003b; Blythe et al. 2010 ) suggesting very
early and direct roles for these proteins in dividing the embryo into prospective
BMP-expressing or -absent territories. Additionally in fish, the accumulation of
nuclear beta-catenin occurs concomitantly with a change in cell division patterns
relative to the body axis as well as slower cell division in the presumptive dorsal
shield region, but a causal relationship between these events has not been estab-
lished (Keller et al. 2008 ).
Although the activation of Nodal and Sia1/2 appears to mediate many of the
functions of maternal beta-catenin signaling, other less characterized pathways are
likely required as well. One other beta-catenin target gene, nodal homolog 3.1
D.W. Houston