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At this point in the development of the fly, the
anterior-posterior axis is clearly defined, and the
embryo is parceled up into domains of gene expres-
sion that correspond to the different segments of the
animal. The next step requires a set of genes that will
uniquely specify each segment as different from one
another. The genes that control the relative identity of
the different parts of Drosophila were discovered by
Edward Lewis (1978). He found mutants of the fly
that had two pairs of wings instead of the usual
single pair. In normal flies, wings form only on the
second thoracic segment; however, in flies with a
mutation in the ultrabithorax gene, another pair of
wings forms on the third thoracic segment. These
mutations transformed the third segment into another
second segment. Mutations in another one of these
homeotic genes— antennapedia —causes the transfor-
mation of a leg into an another antenna. Elimination
of all of the hox genes in the beetle, Tribolium, results in
an animal in which all parts of the animal look identi-
cal (Stuart et al., 1993) (Figure 2.4). Analysis of many
different types of mutations in this complex have led
to the conclusion that, in insects, the homeotic genes
are necessary for a given part of the animal to become
morphologically different from another part.
The Homeobox genes in Drosophila are arranged in a
linear array on the chromosome in the order of their
expression along the anterior-posterior axis of the
animal (Figure 2.5). A total of eight genes are organized
on the chromosome as two complexes, the Antenna-
paedia (ANT-C) and Bithorax (BX-C) clusters (Duboule
and Morata, 1994; Gehring, 1993). The Homeobox genes
code for proteins of the homeodomain class of tran-
scription factors and were the original members of this
very large set of related molecules. All of the Homeobox
proteins have a sequence of approximately 60 highly
conserved amino acids. Like other types of transcrip-
tion factors, the Homeobox proteins bind to a consensus
sequence of DNA in the promoters of many other genes
(Gehring, 1993; Biggin and McGinnis, 1997).
How do these genes control segmental identity in
Drosophila ? A good example is the mechanism by
which the BT-X genes control abdominal segment
identity. Insects have three pairs of legs, one on each
of the thoracic segments, but none on the abdominal
segments. The products of the BT-X gene complex are
responsible for suppressing the formation of legs on
the abdominal segments by the repression of a key
regulatory gene necessary for leg formation, the distal-
less gene. Although this kind of simple regulatory
interaction occurs for some aspects of segmental
identity, the Homeobox gene products bind to a rather
short core DNA sequence of just four bases, and there
are likely to be many genes that contain the sequence
Gap genes
FIGURE 2.3 The unique positional identity of the segments in
Drosophila is derived by a program of molecular steps, each of which
progressively subdivides the embryo into smaller and smaller
domains of expression. The oocyte has two opposing gradients of
mRNA for the maternal effect genes; bicoid and hunchback are
localized to the anterior half, while caudal and nanos messages are
localized to the posterior regions. The maternal effect gene products
regulate the expression of the gap genes, the next set of key tran-
scriptional regulators, which are more spatially restricted in their
expression. Orthodenticle (otd), for example, is a gap gene that is
only expressed at the very high concentrations of bicoid present in
the prospective head of the embryo. Specific combinations of the gap
gene products in turn activate the transcription of the pair-rule
genes, each of which is only expressed in a region of the embryo
about two segments wide. The periodic pattern of the pair-rule gene
expression is directly controlled by the gap genes, and along with a
second set of periodically expressed genes, the segment polarity
genes determine the specific expression pattern of the homeotic
genes. In this way, each segment develops a unique identity.
Segment polarity
ing protein gradients of the two gene products (Figure
2.3). The levels of these two proteins determine
whether a second set of genes, the gap genes, are
expressed in a particular region of the embryo. The
gap genes, in turn, control the striped pattern of a third
set of genes, the pair rule genes. Finally, the pattern
of expression of the pair rule genes controls the
segment-specific expression of a fourth set of genes,
the segment polarity genes. This developmental hier-
archy progressively divides the embryo into smaller
and smaller domains with unique identities (Small and
Levine, 1991; Driever and Nusslein-Volhard, 1988).
This chain of transcriptional activations produces the
reproducible pattern of segmentation of the animal
(Figure 2.3).
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