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

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ity of Gdf1 is blocked by co-expression with Wnt antagonists (Skromne and Stern
2001 ). These Gdf1 and Wnt8a signals cooperate to induce Lef1, a Wnt signaling
transcriptional activator, in the PMZ (Skromne and Stern 2001 ) coincident with the
activation of Nodal in the adjacent area pellucida epiblast (Skromne and Stern
2002 ). Nodal itself is required for primitive streak and axis formation (Bertocchini
and Stern 2002 ). Based on shared embryological and molecular characteristics, it
has been speculated that the PMZ epiblast in chick represents the equivalent of the
Nieuwkoop center (Bachvarova et al. 1998 ). However, in birds and likely in mammals

Wnt8a

Gata2

Gdf1

Lef1

Wnt8a

Pitx2 Gdf1

epiblast/hypoblast

marginal zone

Wnt8a

Gdf1+Lef1

endoblast

(beneath)

Hensen’s Node

Gsc, Chrd

Lefty; Cerl

Nodal

Tdgf1

Wnt3 Nodal

epiblast

VE

ParE

ExE

AVE migration

a

p

a

p

hypoblast migration

a

Nodal

Cer

Gdf1

Nodal

Wnt8a

b

beta-cat.

proamniotic

cavity

Wnt

primitive streak

Hensen’s node

Gsc, Chrd

stage Xstage XIIstage 2+

E5.0 E5.5

primitive streak

Fig. 6.9 Models for axis induction signaling in chick and mouse. (a) In the chick blastoderm (left
panel, top/dorsal view, ~stage X, Eyal-Giladi and Kochav 1976 ) the outer marginal zone of the
epiblast expresses Wnt8a in a posterior-to-anterior gradient (purple shading). In the PMZ, Pitx2
(yellow) activates Gdf1 expression (green). Subsequently (middle panel), the newly formed hypo-
blast (below the plane of the page) begins anterior migration and Gdf1 + Wnt8a cooperate to induce
Lef1 in the PMZ and Nodal in the adjacent epiblast. Gata2 is expressed in the anterior marginal
zone and antagonizes Gdf1 long-range. Nodal (magenta) is antagonized by Cerberus (Cer), which
is expressed in the hypoblast. By the initial primitive streak stage (right panel, stage 2+, Hamburger
and Hamilton 1951 ), the anterior migration of the hypoblast and migration of the endoblast beneath
the posterior epiblast removes the inhibition of Nodal and allows feed-forward signaling leading to
primitive streak formation. The same signaling molecules are ex-pressed in the primitive streak
and induce organizer genes in Hensen’s node (dotted circle, Gsc, Chrd) at the anterior tip of the
streak. (b) In the mouse, the earliest asymmetries are the expression of Lefty1 and Cerl (red-brown)
at the tip of the postimplantation AVE (left panel, ~E5.0). These genes are regulated by Nodal
(green) and Tdgf1, and Tdgf1 is regulated by beta-catenin in the absence of secreted Wnt ligand
activity (stop symbol). Lefty1 and Cerl antagonize Nodal and feedback regulation drives AVE
migration towards the proximal egg cylinder on one side (right panel, ~E5.5). Nodal activity is
restricted to the posterior epiblast and is responsible for Wnt3 expression (blue), which in turn
maintains Nodal. These signals cooperate to induce the primitive streak, which induces Hensen’s
node toward the distal tip later in gastrulation. a anterior, p posterior, ExE extraembryonic ecto-
derm, VE visceral endoderm, ParE parietal endoderm

D.W. Houston

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