Abstract
cells along the proximodistal (PD) axis concomitantly with remodelling of the pre-existing stump, making the regenerated legs shorter than normal. In contrast, knockdown of the expanded (ex) or Merlin (Mer) transcripts induced over-proliferation of the regenerating cells, making the regenerated legs longer. These results are consistent with those obtained using rdRNAi during intercalary regeneration induced by leg transplantation. Since these findings fit well with the Ds/Ft steepness model for the determination of organ size, we propose the following model for the control of leg regeneration. A Ds/Ft gradient is responsible for sensing positional disparity and driving proliferation of regenerating cells by activation of the Hippo/Warts pathway. The leg size of regenerates is determined by the steepness of the Ds/Ft gradient, such that growth ceases when the slope of the linear gradient falls below a certain threshold value, which may be determined by an Ex/Mer interaction. Our findings provide additional insight into the longstanding question of how the size and shape of an appendage is determined in metazoa.
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