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gastrulation (Albano et al. 1993 , 1994 ). This suggested that either Activin was not
the endogenous mesoderm-inducing factor, or that the role of the Activin pathway
was not conserved in mammals. This question was only resolved by the identifica-
tion of additional mesoderm inducing molecules.
7.6.1.2 Vg1/Gdf1
A differential screen for maternally expressed genes preferentially localized to the
vegetal pole of the oocyte revealed a second candidate, called vg1 or growth differ-
entiation factor-1 (gdf1) (Rebagliati et al. 1985 ). vg1 encodes a TGF-β molecule
with mesoderm-inducing activity (Weeks et al. 1985 ; Dohrmann et al. 1993 ;
Thomsen and Melton 1993 ). Because of their dorsal mesoderm-inducing activity
and their expression patterns in Xenopus, Activin-B and Vg1/Gdf-1 were good can-
didates for the dorsal mesoderm-inducing signal predicted by the Three Signal
Model (Fig. 7.6b, black arrow) (Dale and Slack 1987b). Vg1/Gdf-1 is also mater-
nally expressed in zebrafish and can induce axial mesoderm when overexpressed
(Helde and Grunwald 1993 ; Dohrmann et al. 1996 ). The chicken orthologue of
Vg1/Gdf-1 is expressed in the PMZ, and it can induce a new primitive streak when
expressed in the lateral marginal zone (Seleiro et al. 1996 ; Shah et al. 1997 ). In the
mouse, Gdf-1 is expressed ubiquitously in the epiblast before gastrulation, consis-
tent with a role in mesoderm induction (Rankin et al. 2000 ; Wall et al. 2000 ).
7.6.1.3 Derriére/Gdf3
A screen for secreted factors expressed in Xenopus embryos uncovered a zygoti-
cally expressed TGF-β molecule closely related to Vg1, called Derriére or Gdf-3
(Sun et al. 1999a). Derriére/Gdf-3 can induce mesoderm and endoderm in animal
caps, and inhibits head formation when overexpressed in the dorsal blastomeres.
When injected ventrally, Derriére/Gdf-3 induces a secondary body axis containing
posterior trunk mesoderm, including muscle. This indicates that Derriére/Gdf-3 has
the ability to dorsalize ventral mesoderm, as expected for the dorsalizing signal in
the Three-signal model (Fig. 7.6b, white arrows). Mouse Gdf-3 is ubiquitously
expressed prior to gastrulation (Chen et al. 2006 ).
7.6.1.4 Nodal
In 1993, a retroviral insertion was identified that disrupted a new member of the
TGF-β superfamily in the mouse (Zhou et al. 1993 ). The affected gene was named
nodal because of its expression pattern in the node. It is also expressed in the primi-
tive streak and in the extraembryonic visceral endoderm (Conlon et al. 1994 ). The
chicken nodal orthologue, cNR-1, is expressed in the middle two-thirds of the prim-
itive streak until it is fully extended (Levin et al. 1995 ). Nodal can induce formation
W. Tseng et al.