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to mesoderm induction. Importantly with respect to axis formation, Nieuwkoop and
colleagues showed that the blastula vegetal mass is dorsoventrally patterned, with
only the dorsovegetal cells being able to induce dorsal mesoderm/organizer. This
dorsal signaling center, or “Nieuwkoop center” as it became known (Gerhart et al.
1989 ), was also demonstrated by transplantation of dorsal vegetal cells into
UV-ventralized hosts (or ventrally into normal hosts), resulting in largely non-cell-
autonomous organizer and axis induction (Gimlich and Gerhart 1984 ; Gimlich
1986 ; Kageura 1990 ).
Cortical rotation emerged as the candidate upstream event leading to Nieuwkoop
center formation in dorsovegetal cells, as embryos ventralized by UV-irradiation lack
both Nieuwkoop center and organizer activity (Smith et al. 1985 ; Gerhart et al. 1989 ).
Also, because the extent of mesoderm induction is unchanged in ventralized embryos
(Cooke and Smith 1987 ), a hypothesis was formed that the Nieuwkoop center gener-
ates a distinct dorsalizing signal or a competence modifying signal, which acts along
with a general mesoderm inducer to induce the organizer. This idea became enshrined
in the influential three-signal models of axis formation (Smith et al. 1985 ; Smith
1989 ; Heasman 1997 ). It is now recognized, owing to the work of many labs over
many years, that this “dorsal signal” is not a unique signal at all, but represents an
early and elevated wave of Nodal-related Tgfb signaling that is regulated by dorsally
enriched Wnt/beta-catenin signaling and other maternal factors (see below).
Although many of these studies were conducted using Xenopus embryos, trans-
plantation experiments have shown that localized regions in the blastula-equivalent
stages of the zebrafish and chicken embryo can induce axes non-cell autonomously
(dYSL, Mizuno et al. 1999 ; PMZ epiblast, Bachvarova et al. 1998 ). These regions
also ultimately act through elevated Nodal signaling, either downstream of or in
concert with Wnt/beta-catenin signaling, suggesting that the mechanisms of axis
induction are widely conserved vertebrate development. In mammals however,
Nodal signaling likely precedes obvious Wnt asymmetry and is the main determi-
nant of axis formation, albeit in conjunction with Wnt signaling. In this section, the
roles of early Wnt signaling in establishing dorsal fates in amphibians and fish are
reviewed, along with the conserved but divergent roles of Wnt and Nodal signaling
in regulating organizer formation across vertebrates.
6.3.1 Basic Wnt Signaling Mechanisms
Since its initial discovery as a mammalian oncogene (Nusse and Varmus 1982 ), sig-
naling by the deeply conserved Wnt1 (int-1/wingless (wg)) family of growth factors
has emerged as a central feature of many aspects of animal development and disease.
The reception of Wnt signals and intracellular signal transduction mechanisms has
been extensively studied in vivo in both vertebrate and invertebrate organisms as
well as in tissue culture cells. Although there are many variations that are important
in specific tissues and disease states, three main arms of the pathway are widely
implicated in vertebrate axis formation. These are: (1) the regulation of Ctnnb1
D.W. Houston