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

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but accumulating molecular evidence supports a modified version of the Nieuwkoop
model (Fig. 6.12b and c). This support is based on three major findings:

1. that BMP antagonists, Noggin, Chordin and Follistatin act as endogenous neural
   inducers, and induce exclusively anterior neural fate in competent ectoderm (see
   Sect. 6.4, Smith and Harland 1992 ; Hemmati-Brivanlou et al. 1994 ; Sasai et al.
   1994 ),


2. the identification of “transforming” molecules, such as FGFs, Wnts, Nodals, and
   retinoids, which posteriorize anterior tissue (reviewed in Stern 2005 ) but do not
   directly neuralize ectoderm per se, and,


3. the elucidation of proposed “anterior stabilizing” signals (Fraser and Stern
   2004 ). These are mediated by continuing BMP antagonism (Hartley et al. 2001 ),
   Wnt antagonism by inhibitors such as Frzb1 and Dickkopf1 (Leyns et al. 1997 ;
   Wang et al. 1997 ; Glinka et al. 1998 ), multifunctional antagonism by members
   of the Cerberus/DAN family of proteins (Bouwmeester et al. 1996 ) and the feed-
   back Nodal antagonism by Lefty1 (Thisse et al. 2000 ; Cheng et al. 2000 ). These
   molecules are expressed prior to gastrulation in the extraembryonic endoderm
   (anterior visceral endoderm (AVE)/hypoblast/foregut endoderm), and during
   gastrulation in the anterior definitive endoderm and prechordal plate, providing
   signals that initiate and stabilize anterior pattern, respectively.

blastopore

BMP antagonism:

activation

anti-BMP/Wnt; forebrain

Wnt3

Wnt8

blastopore

Wnt

antagonists

posterior Wnt gradient:

anterior Wnt inhibition:

transformation

f.b.

m.b.

h.b.

s.c.

blastopore

f.b.

m.b.

h.b.

s.c.

f.b.

h.b.m.b.

s.c.h.b.

Nieuwkoop’s ectodermal fold

experiments

ep.

a neural/n.p.b.

p

ab

epidermis

d

v

FGF

c

neural

plate

Fig. 6.12 Models for anteroposterior axis patterning in vertebrates. (a) Depiction of Nieuwkoop’s
ectodermal fold implantation experiments (Nieuwkoop 1952 ; Nieuwkoop and Nigtevecht 1954 ).
Dorsal posterior view of a neurula stage amphibian embryo; neural fate is represented as a gradient
from light-to-dark with darker color indicating more posterior fates; the epidermis is yellow. The
implanted folds are shown as boxes, divided to show the approximately position of induced neural
fates. Each fold is characterized by a distal epidermal portion (ep.) bounded by general neural/
neural plate border (activated tissue); this is followed proximally by graded neural fates, reflecting
the hypothesized influence of a transforming gradient (as opposed to a distinct inducer at each AP
level). (b) Molecular interpretation of Nieuwkoop’s model. In the gastrula, neural induction is
accomplished by BMP antagonism, which induces neural tissue with forebrain character. (c)
During later gastrulation, the expression of Wnts directly induces posterior fates in anterior neural-
fated tissue in a dose-dependent fashion. FGF signaling is required in a permissive role. Wnt
antagonists expressed in the anterior mesendoderm limit the extent of Wnt signaling and the ante-
rior remains forebrain

D.W. Houston

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