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Nervous system
Dorsal
Normal embryo
A
Ventral
UV
B
Ventralized
embryo
Li
Hyperdorsalized
embryo
C
FIGURE 1.19 Chordin expression in a frog embryo. The arrow
points to the organizer region at the dorsal lip of the blastopore, and
the blue label shows the cells of the pre-gastrula that express the
gene chordin. (From Sasai et al., 1994)
Extract polyA mRNA
Normal embryo
UV
D
Organizer
region
Normal embryo
activin receptor that when misexpressed in embryos
would interfere with normal endogenous activin sig-
naling (Hemmati-Brivanlou and Melton, 1994) (Figure
1.20). To the surprise of these investigators, interfer-
ing with activin signaling not only disrupted normal
mesoderm development, but it also induced the cells
of the animal cap to develop as neurons without any
additional neural-inducing molecule. They proposed
that activin—or something like it—normally inhibits
neural tissue from differentiating in the ectoderm.
They also suggested that perhaps neural induction
occurred by inhibiting this neural inhibitor; in other
words, that the Spemann organizer secretes factors
that antagonize a neural inhibitor. These results led to
the idea that neural tissue is in some way the default
state of the ectoderm and that it must be actively inhib-
ited by activin-like proteins of the TGF-b family. The
idea that the ectoderm is actively inhibited from
becoming neural tissue has some additional support.
In 1989, two groups (Godsave and Slack, 1989; Grunz
and Tacke, 1989) reported that dissociation of the
animal cap cells prior to neural induction resulted in
most of the cells differentiating as neurons (Figure
1.21). Taking these lines of evidence together, it became
clear that molecules that could inhibit activin signal-
ing would make good neural inducers. Since follistatin
was already known to inhibit TGF-b signaling from the
studies of these factors in the reproductive system,
Melton and colleagues tested whether follistatin could
act as a neural inducer. They found that indeed folli-
statin could cause a secondary axis when misex-
pressed, and recombinant follistatin could induce
neural tissue from animal caps. Follistatin is also
UV
E
cDNA
noggin
protein
Neural
genes
noggin cDNA
+
A
FIGURE 1.18 The identification of noggin as a neural inducer
used an expression cloning strategy in Xenopus embryos. A. Normal
development of a Xenopus embryo. B. UV light treatment of the early
embryo inhibits the development of dorsal structures by disrupting
the cytoskeleton rearrangements that pattern the dorsal inducing
moelcules prior to gastrulation (ventralized). C. Lithium treatment
of the early embryo has the opposite effect; the embryo develops
more than normal dorsal tissue (i.e. hyperdorsalized). D. If messen-
ger RNA is extracted from the hyperdorsalized embryos and injected
into a UV-treated embryo, the messages encoded in the mRNA can
“rescue” the UV-treated embryo and it develops relatively normally.
E. Similarly, cDNA from the organizer region of a normal embryo
can rescue a UV-treated embryo. The noggin gene was isolated as a
cDNA from the organizer region that could rescue the UV-treated
embryo when injected into the embryo, and subsequently, recombi-
nant protein was made from this cDNA and shown to induce neural
tissue from isolated animal caps, without any induction of meso-
dermal genes. Neural tissue is shown in red in all panels.
listatin works as a regulatory factor by binding to and
inhibiting activin, a member of the TGT-b family of
proteins that controls FSH secretion from the pituitary
gland. During a screen for mesoderm-inducing factors,
Melton found that activin could act as a mesoderm
inducer. To study the mechanism of activin action
on mesoderm induction, he constructed a truncated
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