Nadine McGinnis

Hox protein mutation and macroevolution of the insect body plan

A fascinating question in biology is how molecular changes in developmental pathways lead to macroevolutionary changes in morphology. Mutations in homeotic (Hox) genes have long been suggested as potential causes of morphological evolution, and there is abundant evidence that some changes in Hox expression patterns correlate with transitions in animal axial pattern. A major morphological transition in metazoans occurred about 400 million years ago, when six-legged insects diverged from crustacean-like arthropod ancestors with multiple limbs. In Drosophila melanogaster and other insects, the Ultrabithorax (Ubx) and abdominal A (AbdA, also abd-A) Hox proteins are expressed largely in the abdominal segments, where they can suppress thoracic leg development during embryogenesis. In a branchiopod crustacean, Ubx/AbdA proteins are expressed in both thorax and abdomen, including the limb primordia, but do not repress limbs. Previous studies led us to propose that gain and loss of transcriptional activation and repression functions in Hox proteins was a plausible mechanism to diversify morphology during animal evolution. Here we show that naturally selected alteration of the Ubx protein is linked to the evolutionary transition to hexapod limb pattern.

The Drosophila Hox Gene Deformed Sculpts Head Morphology via Direct Regulation of the Apoptosis Activator reaper

Hox proteins control morphological diversity along the anterior-posterior body axis of animals, but the cellular processes they directly regulate are poorly understood. We show that during early Drosophila development, the Hox protein Deformed (Dfd) maintains the boundary between the maxillary and mandibular head lobes by activating localized apoptosis. Dfd accomplishes this by directly activating the cell death promoting gene reaper (rpr). One other Hox gene, Abdominal-B (Abd-B), also regulates segment boundaries through the regional activation of apoptosis. Thus, one mechanism used by Drosophila Hox genes to modulate segmental morphology is to regulate programmed cell death, which literally sculpts segments into distinct shapes. This and other emerging evidence suggests that Hox proteins may often regulate the maintenance of segment boundaries.

Developmental and molecular analysis of Deformed; a homeotic gene controlling Drosophila head development.

The characteristic morphology of many elements of the Drosophila body plan is crucially dependent upon the proper spatial expression of homeotic selector genes. The Deformed locus, which we isolated by virtue of its homology to the homeo box, is a candidate for a homeotic selector in the head region of the developing embryo. Here we show that null mutants of Deformed result in a loss of pattern elements derived from the maxillary and mandibular segments, and a duplication of a cuticular element of the larval head skeleton. Molecular analysis of the locus shows that Dfd transcripts are encoded in five exons distributed over 11 kb. The major transcript of 2.8 kb contains a 1758‐bp open reading frame that would translate to yield a 63.5‐kd protein containing a homeo domain and conspicuous regions of monotonic amino acid sequences. The Dfd protein exhibits extensive homology to a protein encoded by a Xenopus homeo box gene, Xhox 1A, suggesting that the Xenopus gene is the frog homologue of Dfd.