Morphogens, such as Decapentaplegic (Dpp) in the fly imaginal discs, form graded concentration profiles that control patterning and growth of developing organs. In the imaginal discs, proliferative growth is homogeneous in space, posing the conundrum of how morphogen concentration gradients could control position-independent growth. To understand the mechanism of proliferation control by the Dpp gradient, we quantified Dpp concentration and signaling levels during wing disc growth. Both Dpp concentration and signaling gradients scale with tissue size during development. On average, cells divide when Dpp signaling levels have increased by 50%. Our observations are consistent with a growth control mechanism based on temporal changes of cellular morphogen signaling levels. For a scaling gradient, this mechanism generates position-independent growth rates.
Morphogens are secreted signalling molecules that control the patterning and growth of developing organs. How morphogens regulate patterning is fairly well understood; however, how they control growth is less clear. Four principal models have been proposed to explain how the morphogenetic protein Decapentaplegic (DPP) controls the growth of the wing imaginal disc in the fly. Recent studies in this model system have provided a wealth of experimental data on growth and DPP gradient properties, as well as on the interactions of DPP with other signalling pathways. These findings have allowed a more precise formulation and evaluation of morphogenetic growth models. The insights into growth control by the DPP gradient will also be useful for understanding other morphogenetic growth systems.
Schwank et al. challenge the temporal growth model with an experiment in which Dpp signal transduction is abrogated. They claim that in this condition, cellular Dpp signaling levels do not increase over time but that cells do grow normally. We repeated this experiment and observed an increase of signaling over time. The results are consistent with a temporal model of growth control.I n a recent study (1) we found that, in the Drosophila wing disc, the cell proliferation rate correlates with the relative temporal increase in signaling levels of the morphogen Dpp and that, therefore, relative temporal changes in signaling could control proliferation [among other possibilities discussed in the supporting online material (SOM) of (1) In our recent paper, we did study a similar experimental condition: a brk XA dpp d12/d14 mutant (1). We found that the output of the Dpp signaling pathway, as measured by the transcriptional reporter dad-RFP, was strongly positiondependent and did increase over time in this condition [SOM of (1)
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