The Questions of Developmental Biology

During early python development, Hoxc-6
is not expressed in the absence of Hoxc-8, so the
forelimbs do not form. Rather, the combination of
Hoxc-6 and Hoxc-8 is expressed for most of the
length of the organism, telling the vertebrae to
form ribs throughout most of the body (Figure
22.9; Cohn and Tickle 1999).
The hindlimb buds do begin to form in pythons, but they do not make anything more than
a femur. This appears to be due to the lack of sonic hedgehog expression by the limb bud
mesenchyme. Sonic hedgehog is needed both for the polarity of the limb and for maintenance of
the apical ectodermal ridge (AER). Python hindlimb buds lack the AER. Interestingly, the
phenotype of the python hindlimb resembles that of mouse embryos with loss-of-function
mutations of sonic hedgehog (Chiang et al. 1996).
Hox genes and atavisms.
As we have seen, disruptions of the Hox genes can change
one type of vertebra into another type. In some instances, the mutation
of a Hox gene can produce "atavistic" conditions, wherein the
organism resembles an earlier evolutionary stage. Deletion or
misregulation of the Hoxa-2 genes in mice, for instance, results in a
partial transformation of the second pharyngeal arch into a copy of the
first pharyngeal arch. The mutant fetuses lack the stapes and styloid
bones formed from the second arch, but have extra malleus, incus,
tympanic, and squamosal bones. They also possess a rodlike cartilage
that has no counterpart in normal mice, but looks like the
pterygoquadrate cartilage thought to have been present in therapsids,
the reptilian ancestors that gave rise to the mammals (Figure 22.10;
Rijli et al. 1993; Lohnes et al. 1994; Mark et al. 1995). Thus, major
evolutionary changes can be correlated with the alteration of Hox
gene expression in different parts of the embryo.