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

1162 Chapter 21: Development of Multicellular Organisms
throughout the life of the fly, long after the signals that induced and refined it have
disappeared. The segment borders will form at the posterior edge of each such
Engrailed stripe (Figure 21–22).
In addition to regulating the segment-polarity genes, the products of pair-rule
genes collaborate with those of gap genes to induce the precisely localized activation
of a further set of genes—originally called homeotic selector genes and now
often called Hox genes, for reasons that will become clear shortly. It is the Hox
genes that permanently distinguish one segment from another. In the next section,
we examine these important genes in detail and consider their role in cell
memory; we shall see that this role is critical in a wide range of animals, including
ourselves.
10-hour embryo
100 µm
Hox Genes Permanently Pattern the A-P Axis
As animal development proceeds, the body becomes more and more complex.
But again and again, in every species and at every level of organization, we find
that complex structures are made by repeating a few basic themes, with variations.
Thus, a limited number of basic differentiated cell types, such as muscle
cells or fibroblasts, recur with subtle individual variations in different sites. These
cell types are organized into a limited variety of tissue types, such as muscle
or tendon, which again are repeated with subtle variations in different regions
of the body. From the various tissues, organs such as teeth or digits are built—
molars and incisors, fingers and thumbs and toes—a few basic kinds of structure,
repeated with variations.
Wherever we find this phenomenon of modulated repetition, we can break
down the developmental biologist’s problem into two kinds of questions: what is
the basic construction mechanism common to all the objects of the given class,
and how is this mechanism modified to give the observed variations in different
animals? The segments of the insect body provide a good example. We have
thus far sketched the way in which the rudiment of a single body segment is constructed
and how cells within each segment become different from one another.
We now consider how one segment becomes determined, or specified, to be different
from another.
The first glimpse of the answer to this problem came over 80 years ago, with
the discovery of a set of mutations in Drosophila that cause bizarre disturbances
in the organization of the adult fly. In the Antennapedia mutant, for example, legs
sprout from the head in place of antennae, whereas in the Bithorax mutant, portions
of an extra pair of wings appear where normally there should be the much
smaller appendages called halteres (Figure 21–23). These mutations transform
parts of the body into structures appropriate to other positions, and they are
called homeotic mutations (from the Greek “homoios,” meaning similar) because
the transformation is between structures of a recognizably similar general type,
changing one kind of limb, or one kind of segment, into another. It was eventually
discovered that a whole set of genes, the homeotic selector genes, or Hox
genes, serve to permanently specify the A-P characters of the whole set of animal
segments. These genes are all related to one another as members of a multigene
family.
There are eight Hox genes in the fly, and they all lie in one or the other of two
gene clusters known as the Bithorax complex and the Antennapedia complex.
wild type loss of Ubx gain of Ubx
(A) haltere (B) (C)
adult
500 µm
Figure 21–22 The pattern of expression
of Engrailed, a segment-polarity gene.
The Engrailed pattern is shown in a 10-
hour embryo and an adult (whose wings
have been removed in this preparation).
The pattern is revealed by constructing
a strain of Drosophila containing the
control sequences of the Engrailed gene
coupled to the coding sequence of the
reporter LacZ, whose product is detected
histochemically through the brown product
generated by immunohistochemistry
against LacZ (10-hour embryo) or through
the blue product generated by a reaction
that LacZ catalyzes (adult). Note that the
Engrailed MBoC6 pattern, m22.41/22.22 once established, is
preserved throughout the animal’s life.
(Courtesy of Tom Kornberg.)
Figure 21–23 Homeotic mutations.
Ultrabithorax, or Ubx, is one of three
genes in the Bithorax gene complex (a
Hox gene cluster). Ubx is responsible for
all of the differences between the second
and third thoracic segments. (A, B) Ubx
loss-of-function mutations transform the
haltere-bearing segment (A) into a wingbearing
segment, resulting in four-winged
flies (B). (C) Ubx gain-of-function in the
second thoracic segment transforms
this wing-bearing segment into a halterebearing
segment, resulting in wingless flies.
(Courtesy of Richard Mann.)