Historical Constraints and the Evolution of Development 1103
for similarity of action soon followed, thus securing the argument for meaningful
morphogenetic conservation across at least 530 million years, and almost maximal
bilaterian separation.
The vertebrate Hox genes also exhibit the crucial colinearity between sequential
order on the chromosome and site of action along the body's A-P axis. Moreover, and
most impressively, several early studies confirmed that the familiar arthropod rules
for loss-of-function (anterior structures move back) and gain-of-function (posterior
structures more forward) generally apply to vertebrate development as well (although
unique and non-homeotic effects have also been demonstrated, as in Pollock et al.,
1995). For example, in loss-of-function experiments, Le Mouellic et al. (1992)
deactivated the mouse Hoxc- 8 gene (previously, as in this 1992 paper, called Hox-
3.1) and noted anteriorization of vertebral form throughout a substantial region of the
body axis extending from the 14th to the 21st vertebra (T7 to LI). In the most striking
effect, a supernumerary pair of ribs (characteristic of thoracic vertebrae) grew on the
first lumbar vertebra. In general, "vertebrae and ribs displayed more or less
pronounced transformations, turning them into structures resembling those
characteristic of the adjacent anterior segment" (1992, p. 251).
Rancourt et al. (1995) also observed anteriorization towards the adjacent
segment in mice with disrupted expression of Hoxb- 5 and Hoxb-6. The first thoracic
segments often lost their rib heads and grew altered lateral processes "making them
indistinguishable from C7" (1995, p. 112). Since, with the rarest exceptions of 6 to 9
in sloths and 6 in manatees, all mammals possess 7 cervical vertebrae (yes, including
giraffes, who grow very long cervicals but don't augment their number!), this
homeotic transformation of the first thoracic to the form of a supernumerary (or
eighth) cervical seems as curiously in violation of basic taxonomic signatures as the
more famous four-winged and eight-legged Drosophila.
In an interesting temporal analog, illustrating the common coincidence of spatial
and temporal ordering in the expression of Hox sequences, Dolle et al. (1993)
disrupted the most 5' (and therefore last acting) Hoxd- 13 gene in mice, and noted a
variety of effects upon the limbs, all interpretable as neotenic changes expressing
developmental delays evoked by deactivating the last stages of a normal temporal
sequence in ontogeny. (I particularly appreciate Dolle et al.'s conscious linkage of
these genetic results to the classical data on heterochrony (see Gould, 1977b) as a
morphological approach to questions about the regulation of development.) Dolle et
al. (1993, p. 438) note an interesting relationship between these genetic results and
common pathways of evolutionary change in heterochronic phenotypes, thus
invoking this chapter's central theme of positive constraints based on internal
channels:
In such evolutionary modifications, the first skeletal elements to be lost are
usually those that are formed last during the establishment of the
chondrogenic pattern. In Hoxd- 13 mutants, the missing skeletal elements are
precisely those that appear last during the development of the