Vertebrate Development Maternal to Zygotic Control (Advances in Experimental Medicine and Biology)

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expression of a nodal-transgene in the distal epiblast depends on FoxH1, a transcrip-
tional effector of Nodal signaling that binds to and activates an Activin/Nodal
Response Element in the first intron (Saijoh et al. 2000 ; Yamamoto et al. 2001 ; Norris
et al. 2002 ). Finally, nodal expression is restricted to the proximal epiblast in the
absence of the essential Nodal co-receptor, Cripto (Liguori et al. 2008 ). The residual
expression of nodal in Cripto−/− mutants depends upon a related co- receptor called
Cryptic, since Cripto−/−;Cryptic−/− double mutants are indistinguishable from nodal
null mutants (Chu and Shen 2010 ). Nodal expression is restricted to the proximal
epiblast of gdf3−/− embryos and gdf1−/−;gdf3−/− double mutants, consistent with the
idea that Vg1 orthologues act to induce nodal expression (Chen et al. 2006 ; Andersson
et al. 2007 ). Another signal is likely acting in parallel to Gdf1 and Gdf3, since low
levels of nodal are still expressed in gdf1−/−;gdf3−/− double mutants, and neither gene
is expressed in the ExE, the source of the initial nodal-inducing signals (Fig. 7.10a).

Xenopus Zebrafish

a b

Maternal Sqt

(DVR1)

(Activin)

Ndr1/Sqt

Ndr2/Cyc

Fgf Sqt /Cyc

Mxtx2

(T-box?)

Mesendoderm

Activin

Vg1

Fgf Xnr

VegT

Mesoderm

Fig. 7.9 Mesoderm and endoderm inducing pathway in frogs and fish. (a) In Xenopus, the mater-
nally expressed T-box transcription factor, VegT induces expression of the xnr genes (solid red
arrow), acting in parallel with maternally expressed Activin and Vg1 (solid white arrow). Xnr
signals induce a positive feedback loop (curved white arrow), which acts via a conserved Activin/
Nodal Response Element in the first intron of xnr1. Xnr signals act in parallel with Fgf signals to
specify mesoderm (black arrows). Activin acts independently of the Xnr genes to induce mesoder-
mal gene expression (long white arrow). Direct regulation of Fgf by VegT (dashed red arrow) and
the Xnrs (dashed yellow arrow) is possible, but has not been established. (b) In zebrafish, Maternal
Ndr1/Sqt, perhaps acting in parallel with maternally expressed Activin and DVR-1, induces
zygotic expression of ndr1/sqt (large black arrow). The transcription factor Mxtx2 is also required
to induce ndr1/sqt and ndr2/cyc expression in the YSL (red arrow). Ndr1/Sqt and Ndr2/Cyc in the
YSL induces expression of ndr1/sqt and ndr2/cyc in the overlying marginal blastomeres (short
black arrow), in a manner that requires a conserved Activin/Nodal Response Element in the first
intron of both genes. Ndr1/Sqt and Ndr2/Cyc expression induces a positive feedback loop (curved
white arrow), and expression of Fgf3 and Fgf8. Ndr1/Sqt, Ndr2/Cyc and Fgf signals act in parallel
to specify mesendodermal fates (short black arrows). Fgf signals also induce expression of com-
ponents of the Nodal signal transduction pathway, creating a self-reinforcing loop of expression
between Nodal and Fgf signals. It is possible that Ndr1/Sqt and Ndr2/Cyc in the YSL also act
directly to induce expression of Fgf3 and Fgf8 in the margin (dashed yellow arrow)

7 Establishment of the Vertebrate Germ Layers