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gists continue to refine the model, the overall scheme
from BMP antagonism to proneural gene expression is
beginning to take shape.
Epidermal
Neural
BMP
Noggin
Chordin
Follistatin
Wnt
FGF
SUMMARY
Frz
FGFR
Classical embryology led to the conclusion that the
nervous system arises during development through an
inductive conversion of ectodermal cells to neural
tissue via the Spemann organizer. In the past 15 years,
a concerted effort has identified the molecular basis
of this neural tissue induction as an inhibition of a
tonic BMP-mediated repression. In both Drosophila and
Xenopus, the antagonism of the TGF-beta-like factors
BMP/dpp are critical in defining the neurogenic
region of the embryo, and a number of “neural induc-
ers,” BMP antagonists, are found in the organizer. The
antagonism of BMP is both necessary and sufficient
for nervous system induction; however, in Drosophila,
the delamination of neuroblasts from the neurogenic
region requires a second signaling system, the Notch/
Delta system, to regulate the expression and function
of a proneural bHLH class of transcription factors. The
Notch/Delta/proneural system is conserved in verte-
brates, thus, it is likely that the overall system of early
neural “induction” and commitment to neural tissue is
largely conserved across all animals.
Smad
Nucleus
Smad
Gata
Sox
Msx
Pro-
neural
bHLH
genes
Sox
FIGURE 1.34 The current model of neural induction. The default
condition of the ectoderm is to make epidermis, through the activa-
tion of the BMP pathway. BMP in the ectoderm stimulates the recep-
tor to activate a set of intracellular proteins (Smad; see Box) that
regulate transcription of genes such as Gata and Msx . The resulting
Msx and Gata proteins inhibit Sox transcription, and the tissue
becomes epidermis. If the BMP signal is blocked by one of the many
inhibitors in the organizer, the Smad pathway is inactivated, and Sox
are made in the cells. The Sox can then directly activate the proneural
gene transcription to cause the cells to develop as nervous system.
FGF may provide an alternate pathway that directly activates Sox
expression, or might also work to inhibit the Smad signal (see Box).
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