Wild-type adult wing and haltere. Image courtesy of R. Mann, Columbia University, New York, USA.

How organ size is controlled and, in particular, how homologous organs acquire different sizes, is poorly understood. By studying two homologous flight appendages of Drosophila melanogaster — wings and the much smaller halteres, which are needed for balance during flight — Crickmore and Mann have uncovered a mechanism by which the Hox 'selector' gene Ultrabithorax (Ubx) controls organ size. It functions by regulating the amount and distribution of the morphogen Decapentaplegic (Dpp).

The reason for examining these two organs is that all of the differences between wing and haltere development, including size, are controlled by the Ubx gene — when Ubx is removed from haltere cells, a wing forms instead. The authors first confirmed that Ubx limits the size of a haltere in a cell-non-autonomous manner, which indicates the involvement of morphogen-mediated pathways.

Crickmore and Mann then focused their attention on the morphogen Dpp, which promotes growth in both wings and halteres. Dpp is produced by cells that form a stripe along the middle of wings and halteres. Compared with wings, the width of the stripe of cells that expressed dpp in halteres was much narrower and expression was less intense. The authors also found differences in the pattern of the Dpp gradient between halteres and wings.

...altering the shape and intensity of morphogen gradients may be a general mechanism by which selector genes affect tissue sizes...

The gradient of Dpp could be modified by varying the expression pattern of the gene encoding the Dpp receptor, Thickveins (Tkv). When Dpp binds to Tkv, it triggers cell proliferation, but it also results in Dpp being captured for destruction. The authors observed that tkv expression around the source of Dpp was low in wings, which allowed Dpp to diffuse further and form two peaks of Dpp-signalling activity on either side of the stripe. However, tkv expression was high in all haltere cells, thereby trapping Dpp close to the source. Indeed, when tkv was overexpressed in wing cells, the Dpp gradient was narrow and wing size was reduced. By contrast, depletion of Tkv in haltere cells resulted in a broader gradient and increased haltere size.

So, how do Dpp production and mobility relate to Ubx? Dpp and Master of thickveins (Mtv) are both needed to repress tkv expression in the wing. However, the authors showed that Dpp functions as a repressor of mtv expression in Ubx-expressing haltere cells. Therefore, as only one repressor is active, tkv is de-repressed, which restricts the mobility of Dpp. The authors also noticed that in halteres, but not in wings, the Dpp-signalling profile coincides with that of Hedgehog (Hh). Given the overlapping activities and the fact that the transcription of dpp is activated by Hh signalling and repressed by Dpp signalling, they postulated that these conflicting inputs in the same cells might contribute to the reduced Dpp production that is observed in halteres compared with wings. This was indeed the case — so, Ubx reduces the production of Dpp by changing where Dpp signalling occurs.

On the basis of their results, the authors suggest the real possibility that “altering the shape and intensity of morphogen gradients may be a general mechanism by which selector genes affect tissue sizes in animal development.”