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from the progenitor cells, by inhibiting the proneural
genes as described above for Drosophila . As for the
bHLH genes, the Notch/Delta signals are used in ver-
tebrates in a process analogous to that of Drosophila .
expressed prior to neural induction in the ectoderm,
but it becomes restricted to the neural ectoderm at mid-
gastrulation. Overexpression of SoxD causes neural dif-
ferentiation in animal caps as well as in nonneural
ectoderm in the embryo, similar to that observed from
NeuroD (Mizuseki et al., 1998) (Figure 1.33). Another
Sox gene, Sox2 , has a more restricted pattern of expres-
sion, and is expressed in the presumptive neural
ectoderm from the late blastula onwards. Sasai and
colleagues have found that overexpression of a
dominant negative form of Sox2 blocks the effects of
neural-inducing factors, and inhibits nervous system
formation. The relative position of Sox2 or SoxD in the
overall mechanism of neural induction is shown
schematically in Figure 1.34. BMPs activate the Smad
pathway, which inhibits SoxD/2 gene expression.
Noggin, chordin, or follistatin block this pathway
and allow SoxD/2 expression, which leads to proneural
gene expression in the cells. FGF receptor activation
may be an additional direct activator of SoxD/2 expres-
sion. Although the details of the relationships among
these genes will likely change as developmental biolo-
Finally, we would like to link up the processes of
neural induction, covered earlier in the chapter, with
the proneural bHLH /Notch pathway genes discussed
in the second half of the chapter. To look for links
between these processes, Sasai and colleagues used dif-
ferential screening for genes upregulated in the animal
caps after chordin treatment. One family of genes
found in this type of screen, members of the Sox family,
were found to be expressed very early in neural plate,
soon after induction. The Sox proteins are transcription
factors that contain a high mobility group (HMG)
domain and bind to DNA directly. SoxD is a gene
2-cell embryo
FIGURE 1.33 SoxD overexpression causes ectopic neural differentiation. A. SoxD is injected into the right
blastomere of a two-cell embryo (red), and the embryo is allowed to develop to the neural plate stage. B. Epi-
dermis fails to develop in a large region of the right side as indicated by the lack of keratin (arrows). C. In
place of epidermis on the right side of the embryo, a large region of ectopic neurons develops (labeled with
the proneural gene Neurogenin (Xngnr-1 ). (From Mizuseki et al., 1998)
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