Models to explain how morphogen gradients regulate growth and patterning postulate that cells acquire positional values within a gradient, and that proliferation is stimulated by the detection of differences in these values. However, despite its appeal, this theory has so far lacked experimental support. Rogulja and Irvine reasoned that this could be because previous experiments have focused on longer-term responses, and so decided to study short-term responses to morphogen signals.
Using the fly wing as a model, they devised a method for spatially and temporally controlling gene expression in clones of cells, using a progesterone analogue to activate expression. The morphogen that regulates growth and patterning in the wing is DPP, so the authors made transgenic flies in which a constitutively active form of the DPP receptor, Thick-veins (TKVQ-D), was expressed clonally in the wing. As expected, TKVQ-D expression induces the proliferation of cells in a way that depends on their position along the DPP gradient. But, strikingly, TKVQ-D-expressing cells also induce proliferation in their neighbours, non-cell autonomously. The authors provide several lines of evidence to show that non-autonomous proliferation is induced by the juxtaposition of cells that have different positional values along the DPP gradient. For example, by using different concentrations of the progesterone analogue, they show that non-autonomous proliferation depends on quantitative differences in TKV activation. The authors also made clones of cells in which DPP signalling was inhibited, and showed that non-autonomous proliferation is greatest next to those clones that experience the strongest difference in DPP signal — as expected from the model.
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