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

1160 Chapter 21: Development of Multicellular Organisms
EGG-POLARITY GENE
(Bicoid)
GAP GENE (Krüppel)
PAIR-RULE GENE
(Even-skipped)
SEGMENT-POLARITY
GENE (Hedgehog)
Figure 21–19 Examples of the phenotypes of mutations affecting egg-polarity genes and the three types of
segmentation genes. In each case, the areas shaded in green on the normal larva (left) are deleted in the mutant or are
replaced by mirror-image duplicates of the unaffected regions. (Modified from C. Nüsslein-Volhard and E. Wieschaus, Nature
287:795–801, 1980. With permission from Macmillan Publishers Ltd.)
a morphogen and activates different sets of genes at different positions along the
A-P axis: some gap genes are only activated in regions with high levels of Bicoid,
others only where levels of Bicoid are lower. After the gap gene products refine
their positions by mutual repression, they provide a second tier of positional signals
that act more locally to regulate finer details of patterning. Gap genes act by
controlling the expression of yet other genes, including the pair-rule genes. The
pair-rule genes, in turn, collaborate with one another and with the gap genes to
set up a regular, periodic pattern of expression of the segment-polarity genes,
MBoC6 m22.37/22.18
which collaborate with one another to define the internal pattern of each individual
segment (Figure 21–20).
The initial steps in creation of the segmental pattern occur before cellularization
of the syncytial blastoderm and are governed by the combinatorial effects of
transcription regulators, as discussed in detail in Chapter 7 for the regulation of
the expression of the pair-rule gene Even-skipped (see pp. 394–396). After cellularization,
the segment-polarity genes further subdivide each segment into smaller
domains. A large subset of the segment-polarity genes codes for components of
two signaling pathways—the Wnt pathway and the Hedgehog pathway, including
the secreted signal proteins Wingless (the first-named member of the Wnt family)
and Hedgehog. (The Hedgehog pathway was first discovered through study
of Drosophila segmentation, and it takes its name from the prickly appearance
of the surface of the Hedgehog mutant embryo.) Wingless and Hedgehog are synthesized
in different bands of cells that serve as signaling centers within each segment.
The two proteins mutually maintain each other’s expression, while regulating
the expression of genes such as Engrailed in neighboring cells (Figure 21–21).
In such a manner, a series of sequential inductions creates a fine-grained pattern
of gene expression within each segment.
Egg-Polarity, Gap, and Pair-Rule Genes Create a Transient Pattern
That Is Remembered by Segment-Polarity and Hox Genes
The gap genes and pair-rule genes are activated within the first few hours after fertilization.
Their mRNA products initially appear in patterns that only approximate
the final picture; then, within a short time, this fuzzy initial pattern resolves itself
into a regular, crisply defined system of stripes. But this pattern itself is unstable