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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will differentiate into blood (a ventral mesodermal tissue) when diverted from
their original fate by exposure to intermediate concentrations of Nodal and high
concentrations of BMP. Similarly, mouse or human embryonic stem cells can be
coaxed to generate specific cell types by exposing them in culture to appropriate
combinations of signal molecules. In this way, the insights gained through studies
of animal development can be used to generate the cell types needed for regenerative
medicine, as we discuss in the next chapter.
The Insect Dorsoventral Axis Corresponds to the Vertebrate
Ventral-Dorsal Axis
The signaling systems that pattern the D-V axis in Drosophila and in vertebrates
are similar. In Drosophila, as we saw, Dpp and its inhibitor Sog are responsible,
whereas in vertebrates, BMP and its inhibitors Chordin and Noggin do the job.
Dpp is a member of the BMP family, while Sog is a homolog of Chordin. Both in
flies and frogs, high levels of the inhibitors define the region that is neurogenic,
and high levels of BMP/Dpp activity define the region that is not. These and other
molecular parallels strongly suggest that this aspect of body patterning has been
conserved in evolution from insects to vertebrates. Curiously, however, the axis is
inverted: dorsal in the fly corresponds to ventral in the vertebrate (Figure 21–31).
At some point in evolution, it seems that the ancestor of one of these classes of
animals took to living life upside-down.
Hox Genes Control the Vertebrate A-P Axis
The conservation of developmental mechanisms between Drosophila and vertebrates
extends beyond the D-V signaling system. Hox genes are found in almost
every animal species studied, where they are often grouped in complexes similar
to the insect Hox complex. In mice and humans, for example, there are four such
complexes—called the HoxA, HoxB, HoxC, and HoxD complexes—each on a different
chromosome. Individual genes in each complex can be recognized by their
sequences as counterparts of specific members of the Drosophila set. Indeed,
mammalian Hox genes can function in Drosophila as partial replacements for the
corresponding Drosophila Hox genes. It appears that each of the four mammalian
Hox complexes is, roughly speaking, the equivalent of one complete insect
Hox complex (that is, an Antennapedia complex plus a Bithorax complex) (Figure
21–32).
The ordering of the genes within each vertebrate Hox complex is essentially the
same as in the insect Hox complex, suggesting that all four vertebrate complexes
originated by duplications of a single primordial complex and have preserved its
basic organization. Most tellingly, when the expression patterns of the Hox genes
are examined in the vertebrate embryo, it turns out that the members of each
complex are expressed in a head-to-tail series along the axis of the body, just as
they are in Drosophila. As in Drosophila, vertebrate Hox gene expression patterns
are often aligned with vertebrate segments. This alignment is especially clear in
the hindbrain (see Figure 21–32), where the segments are called rhombomeres.
The products of the vertebrate Hox genes, the Hox proteins, specify positional
values that control the A-P pattern of parts in the hindbrain, neck, and trunk (as
well as some other parts of the body). As in Drosophila, when a posterior Hox gene
is artificially expressed in an anterior region, it can convert the anterior tissue to
mouth
INSECT
circulatory system gut DORSAL central nervous system gut
central nervous system
anus
VENTRAL
mouth
circulatory system
anus
VERTEBRATE
Figure 21–31 The vertebrate body plan
as a dorsoventral inversion of the insect
body plan. Note the correspondence with
regard to the circulatory system as well as
the gut and nervous system. In insects,
the circulatory system is represented by
a tubular heart and a main dorsal blood
vessel, which pumps blood out into the
tissue spaces through one set of apertures
and receives blood back from the tissues
through another set. Unlike vertebrates,
insects have no system of capillary vessels
to contain the blood as it percolates
through the tissues. Nevertheless, heart
development depends on homologous
genes in vertebrates and insects,
reinforcing the relationship between the
two body plans. (After E.L. Ferguson, Curr.
Opin. Genet. Dev. 6:424–431, 1996. With
permission from Elsevier.)