Historical Constraints and the Evolution of Development 1105
Lewis's gradient model for establishing domains of differentiation. Of the genes at the
5' end of the complex, she wrote (1992, p. 188): "Cells in the posterior part of the bud
that will give rise to posterior structures such as a 'little finger' express all the genes,
whereas anterior cells that will give rise to the anterior 'thumb' express only Hox-4.4"
(Hoxd- 9 in modern terminology). These rules, apparently pervasive (at least in
bilaterally symmetrical Bilateria with an A-P axis), also explain several well-known
empirical regularities in the classical literature on experimental embryology. Citing
the correlation of spatial order and temporal sequence, Tickle (1992, p. 188) notes:
"Because activation can proceed in only one direction along the complex, this
explained why manipulations can convert anterior structures into posterior ones, but
never posterior into anterior."
The high degree of sequence similarity often found between homologous
arthropod and vertebrate Hox genes (amounting to near identity of homeodomains in
some cases) leads to the remarkable, but (by now) scarcely surprising, interphylum
substitutability revealed by so many experiments (and further discussed as evidence
for parallelism in the evolution of eyes on pages 1123-1132). Fly Hox genes,
expressed in vertebrates, usually broker the same developmental sequences as their
vertebrate homologs—and vice versa. Needless to say, such experiments yield the
"correct" morphologies for each phylum, thus reinforcing the well-established
conclusion that Hox genes specify proper positions and regulate downstream
cascades, but do not build anatomical structures themselves. If Hox genes worked as
architects as well as specifiers, then the frights of Hollywood horror movies might
become realities, and the fly with a human head might really scream, "please help
me" from the despair of his spider-web prison.
As one example among so many, the Drosophila Hox gene Antennapedia
promotes leg identity, presumably by repressing previously unknown antennal genes.
Casares and Mann (1998) have now identified two antennal determiners, including
homothorax (hth). As one line of evidence, they cloned Meisl, the mouse homolog of
Drosophila hth, and expressed it ectopically in the fly's anal primodium, which
normally develops without expressing any Hox genes. The anal plates of these flies
then grew as antennae. (Most Hox genes suppress antennae, so ectopic expression of
Meisl in Hox domains does not generate antennae in odd places, but induces other
malformations, including markedly truncated legs on the thoracic segments.)
As a person with literary pretensions, I am always fascinated by the sure signal
of scientific progress conveyed by the evolution of a rationalized and simplified
terminology. The original Hox terminologies were eclectic and specific. Students of
Drosophila first identified two clusters of homeotic genes, but could not recognize
them as separated parts of a single ancestral sequence. So they awarded different
names: Antennapedia complex (ANT-C) for genes regulating anterior structures, and
Bithorax complex (BX-C) for genes operating in the fly's rear half. When homologs
of both were detected as a single sequence in beetles, terminology began to coalesce,
and the entire series