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antagonists is clearly required for the development of
much of the nervous system, other factors are likely
involved.
Experiments with chick embryos and ascidians
indicate that at least one of these additional factors is
likely a member of the fibroblast growth factor (FGF)
family of signaling molecules. In the chick embryo,
Streit et al. (2000) found that neural induction actually
occurs prior to gastrulation. Moreover, blocking FGF
signaling with an FGF receptor inhibitor, called
SU5402, prevented this early phase of neural induc-
tion. Evidence from the ascidian embryo further sup-
ports the role of FGF in neural induction. Ascidians are
not vertebrates, but before becoming a sessile adult,
they have a “tadpole” intermediate form that resem-
bles a simple vertebrate-like larva, with a notochord
and dorsal neural tube. In this animal, BMP antago-
nists like chordin and noggin do not appear to be
involved in the induction of the neural tube. Instead
FGF is the critical factor, as for the chick. Does FGF act
to antagonize the BMP repression of the neural fate in
ectoderm, Noggin, and Chordin? All of the ways in
which these two different signaling pathways interact
with one another are not yet clear. Nevertheless, there
is evidence that the downstream pathway components
activated by FGF inhibit BMP inhibition by phospho-
rylating Smad proteins (see Box). In addition, a
BMP R
Neural
plate
BMP4
Noggin
TGF b R
IMZ
Cb
Chd
Ng
FIGURE 1.23 The current model of neural induction in amphib-
ian embryos. As the involuting mesodermal cells of the IMZ release
several molecules that interfere with the BMP signals between ecto-
dermal cells. Ceberus, chordin, noggin, and follistatin all interfere
with the activation of the BMP receptor by the BMPs in the ectoderm
and thereby block the anti-neuralizing effects of BMP4. In other
words, they “induce” this region of the embryo to develop as neural
tissue, ultimately generating the brain, spinal cord, and most of the
peripheral nervous system.
A
B
C
FIGURE 1.24 Loss of noggin and chordin in developing mice causes severe defects in head development.
Left, wild-type mouse embryo, middle loss of noggin only. Right, loss of both noggin and chordin. From ref
with permission. Note that only mild defects are present in mice deficient in only noggin, but the head is
nearly absent when both genes are knocked out. (From Bachiller et al., 2000)
 
 
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