255evolutionarily maintained, as this relationship exists as reciprocal repression of
EVX1 (activated by BMP signaling) and GSC (Kalisz et al. 2012 ) in human ES
cells. Thus, although the involvement of the well-characterized Ventx proteins is
variable throughout evolution, possibly related to the timing and requirement for
ventral mesoderm in hematopoiesis in early development (Kozmik et al. 2001 ),
there remains an ancient and conserved network of reciprocal repression between
BMPs and organizer genes.
6.5 Anteroposterior Axis Patterning
In general, within the dorsal blastopore/anterior primitive streak, the sequence of
internalizing mesoderm determines anteroposterior character, with anterior mesend-
oderm (anterior definitive endoderm and prechordal plate) being followed by the
chordamesoderm (notochord). Signals from the organizer have long been implicated
in establishing anteroposterior fates along the body axis. This effect was seen in
Spemann and Mangold’s early experiments in which second axes induced by orga-
nizer transplantation often showed varying degrees of completeness at the anterior
end (Spemann and Mangold 1924 ). These results were roughly correlated with the
stage of gastrula from which the donor dorsal lip was taken; earlier lips induced more
complete axes with well-formed heads and later lips induced truncated axes or sec-
ond tails (Spemann 1931 ). These experiments were interpreted to suggest that the
organizer comprised a spatially distinct “head organizer” that would induce forebrain
in the early gastrula, and a “trunk organizer” that would induce hindbrain and spinal
cord in more posterior ectoderm during later gastrulation. The remaining region, the
midbrain, is formed largely by interactions between forebrain and hindbrain.
Work by Nieuwkoop and others later suggested a different model. Implantation of
folded strips of competent animal cap ectoderm at various anteroposterior levels in
the prospective neuroectoderm generated a graded pattern of neural fates in the
implant, with anterior neural/neural plate border tissue forming distally in the implant
and more posterior neural forming proximally (Nieuwkoop 1952 , 1999 ) (Fig. 6.12a).
These observations were interpreted to suggest a neural “activation” step that initi-
ates a tendency toward forebrain differentiation, followed by a “transforming” event
that converts activated anterior neural tissue to more posterior fates (Nieuwkoop
1952 , 1999 ). Earlier experiments had shown that artificial neural induction in urodele
animal caps using nonspecific chemical and physical methods invariably generated
forebrain (Holtfreter 1944 ). Also, explants taken from early prospective neuroecto-
derm showed progressive waves of activation followed by transformation, occurring
from posterior to anterior and coincident with mesoderm internalization (Eyal-Giladi
1954 ). These different activities were found to depend on the nature of the underlying
axial mesoderm, with activation predominating in the prechordal mesoderm and
anterior notochord and transformation predominating in the posterior notochord
(Sala 1955 ). Experimental data have at various times favored one model or the other,
6 Vertebrate Axial Patterning: From Egg to Asymmetry