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How to turn a wing into a haltere - Hox gene targets during metamorphosis

Hox genes are the master regulators that cause different parts of the body to develop into different structures – for example, into mouthparts on the head, but legs on the thorax. It is still not known how Hox genes bring about these complex changes.  In work published recently in the Proceedings of the National Academy of Sciences (USA), we have shown that the set of downstream targets regulated by one Hox gene changes dramatically as development proceeds.

We have studied the Hox gene Ultrabithorax, (Ubx for short) in fruit flies. In all insects, Ubx is active in the hind wings to make them different from the forewings. In flies, this difference is dramatic – the hind wings develop as small round balancing organs called halteres, while the forewings forms the large flat wing blades used for flying.   We have engineered a system that allows us to activate the Ubx gene in developing wing blades, where it would not normally be expressed. If activated throughout development, this causes the wing blades to develop as reduced balloon-like structures resembling halteres, (see picture above).  However, we can also turn Ubx on at precisely controlled times during development, and then measure its effects in the wing with assays that monitor the activity of thousands of other genes in the genome (microarray profiling and quantitative RT-PCR).

We find that the spectrum of genes regulated by Ubx changes dramatically as the animal proceeds through metamorphosis, from larva to pupa to developing adult.  This explains, at least in part, how just one gene can orchestrate such complex changes in the shape and size of an organ.

The Hox gene Ultrabithorax regulates distinct sets of target genes at successive stages of Drosophila haltere morphogenesis, PNAS USA, 108(7): 2855-2860].