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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The genes in the Bithorax complex control the differences among the abdominal
and thoracic segments of the body, while those in the Antennapedia complex control
the differences among thoracic and head segments. Comparisons with other
species show that the same genes are present in essentially all animals, including
humans. These comparisons also reveal that the Antennapedia and Bithorax
complexes are the two halves of a single entity, called the Hox complex, that has
become split in the course of the fly’s evolution, and whose members operate in
a coordinated way to exert their control over the head-to-tail pattern of the body.
The products of the Hox genes, the Hox proteins, are transcription regulators,
all of which possess a highly conserved, 60-amino-acid-long DNA-binding homeodomain
(see p. 376). The corresponding motif in the DNA sequence is called a
“homeobox,” from which, by abbreviation, the Hox complex takes its name. There
are many homeobox-containing genes, but only those located in a Hox complex
are Hox genes.
Hox Proteins Give Each Segment Its Individuality
The Hox proteins can be viewed as molecular address labels possessed by the cells
of each segment: these labels give the cells in each region a positional value—that
is, an intrinsic character that differs according to a cell’s location. If the address
labels in a developing Drosophila segment are changed, the segment behaves
as though it were located somewhere else; if all the Hox genes in an embryo are
deleted, the body segments in the larva will all be alike.
To a first approximation, each Hox gene is normally expressed in those regions
that develop abnormally when that gene is mutated or absent. How does each
Hox protein give a segment its permanent identity? All the Hox proteins are similar
in their DNA-binding regions, but they are very different in the regions that
interact with the other proteins with which the Hox proteins form transcriptional
regulatory complexes. The different protein partners act together with the Hox
proteins to dictate which DNA binding sites will be recognized, as well as whether
the effect on transcription at those sites will be activation or repression. Acting
in this way, the Hox proteins modulate the actions of many other transcription
regulators. Hundreds of genes are under this type of Hox-modulated control,
including genes for cell–cell signaling, transcriptional regulation, cell polarity,
cell adhesion, cytoskeletal function, cell growth, and cell death, all conspiring (in
ways that are not yet understood) to give each segment its distinctive Hox-dependent
character.
Hox Genes Are Expressed According to Their Order in the
Hox Complex
How, then, is the expression of the Hox genes themselves regulated? The coding
sequences of the eight Hox genes in the Antennapedia and Bithorax complexes in
Drosophila are interspersed amid a much larger quantity of regulatory DNA. This
DNA includes binding sites for the products of the egg-polarity and segmentation
genes, thereby serving as an interpreter of the multiple items of spatial information
supplied to it by all these transcription regulators. The net result is that the
particular set of Hox genes transcribed is appropriate for each location along the
A-P body axis.
The pattern of Hox gene expression exhibits a remarkable regularity that suggests
an additional form of control. The sequence in which the genes are ordered
along the chromosome, in both the Antennapedia and the Bithorax complexes,
corresponds almost exactly to the order in which they are expressed along the
A-P axis of the body (Figure 21–24). This hints at some process of gene activation,
perhaps dependent on chromatin structures that propagate along the Hox complexes,
switching on one Hox gene after another according to their order along the
chromosome. The most “posterior” of the Hox genes that are expressed in a cell
generally dominates, driving down expression and activity of the “anterior” genes
and dictating the character of the segment. The gene regulatory mechanisms