Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

MECHANISMS OF PATTERN FORMATION
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Figure 21–25 The role of genes of the Polycomb group. (A) Photograph of
a wild-type Drosophila embryo. (B) Photograph of a mutant embryo defective
for the gene Extra sex combs (Esc) and derived from a mother also lacking
this gene. The gene belongs to the Polycomb group. Essentially all segments
have been transformed to resemble the most posterior abdominal segment.
In the mutant, the pattern of expression of the homeotic selector genes,
which is roughly normal initially, is unstable in such a way that all these genes
soon become switched on all along the body axis. (From G. Struhl, Nature
293:36–41, 1981. With permission from Macmillan Publishers Ltd.)
wild type
no Polycomb activity
this axis in the egg (see Figure 21–17), and it then progresses through zygotic gene
products that further subdivide the D-V axis in the embryo.
Initially, a protein that is produced by follicle cells underneath the future ventral
region of the embryo leads to the localized activation of a transmembrane
receptor, called Toll, on the ventral side of the egg membrane. The various maternal
genes required for this process are called D-V egg-polarity genes. (Curiously,
Drosophila Toll and vertebrate Toll-like proteins also operate in innate immune
responses, as discussed in Chapter 24). The localized activation of Toll controls
the distribution of Dorsal, a transcription regulator of the NFκB family discussed
in Chapter 15. The Toll-regulated activity of Dorsal, like that of NFκB, depends on
the translocation of Dorsal from the cytosol, where it is held in an inactive form,
to the nucleus, where it regulates gene expression (see Figure 15–62). In the newly
laid egg, both Dorsal mRNA and protein are distributed uniformly in the cytosol.
After the nuclei in the syncytial blastoderm have migrated to the surface of the
embryo, but before cellularization (see Figure 21–15), Toll receptor activation on
the ventral side induces a remarkable redistribution of the Dorsal protein. On the
dorsal side, the protein remains in the cytosol, but ventrally it becomes concentrated
in the nuclei, with a smooth gradient of nuclear localization between these
two extremes (Figure 21–26).
Once inside the nucleus, the Dorsal protein acts as a morphogen and turns on
or off the expression of different sets of genes depending on Dorsal’s concentration.
The expression of each responding gene depends on its regulatory DNA—
specifically, on the number and affinity of the binding sites that this DNA contains
for Dorsal and other transcription regulators. In this way, the regulatory DNA
interprets the positional signal provided by the nuclear Dorsal protein gradient,
so as to define a D-V series of territories—distinctive bands of cells that run the
length of the embryo. Most ventrally—where the nuclear concentration of Dorsal
protein is highest—it switches on, for example, the expression of a gene called
Twist, which is specific for mesoderm. Most dorsally, where the nuclear concentration
of Dorsal protein is lowest, the cells switch on a gene called Decapentaplegic
(Dpp). And in an intermediate region, where the nuclear concentration of
Dorsal protein is high enough to repress Dpp but too low to activate Twist, the
cells switch on another set of genes, including one called Short gastrulation (Sog)
(Figure 21–27A).
Products of the genes directly regulated by the Dorsal protein generate in turn
more local signals, which define finer subdivisions along the D-V axis. These signals
act during cellularization and take the form of conventional extracellular
wild type ventralized dorsalized
DORSAL
VENTRAL
100 µm
(A)
100 µm
(B)
MBoC6 m22.45/22.25
Figure 21–26 The concentration gradient
of Dorsal protein in the nuclei of the
blastoderm. In wild-type Drosophila
embryos, the protein is present in the
dorsal cytoplasm and absent from the
dorsal nuclei; ventrally, it is depleted in the
cytoplasm and concentrated in the nuclei.
In a mutant in which the Toll pathway is
activated everywhere and not just ventrally,
Dorsal protein is everywhere concentrated
in the nuclei; the result is a ventralized
embryo. Conversely, in a mutant in which
the Toll signaling pathway is inactivated,
Dorsal protein everywhere remains in the
cytoplasm and is absent from the nuclei;
the result is a dorsalized embryo. (From
S. Roth, D. Stein and C. Nüsslein-Volhard,
Cell 59:1189–1202, 1989. With permission
from Elsevier.)