Regulation of tissue growth by a morphogen gradient: How DPP scales the Drosophila wing.

摘要

Decapentaplegic (DPP) is a morphogen that is essential for both tissue patterning and growth in Drosophila. It is expressed in multiple tissues throughout several stages of development, but the focus of my work is on its function in the wing disc during the larval instars. Although DPP is, expressed in a narrow stripe of cells along the Anterio-Posterior compartment boundary, its function is required for growth in the entire wing disc. DPP is a secreted protein that forms a gradient across a large field of wing disc cells. However, in spite of the non-uniform nature of the DPP signaling profile, growth is stimulated essentially uniformly throughout the disc. How does a non-uniform signal regulate even growth of a tissue? We have now found evidence for an old model proposed to explain this phenomenon. We found that DPP specifies a gradient of positional values in the wing that guides cell proliferation. The most exciting aspect of this finding is that it suggests a link between tissue growth and tissue patterning that has been speculated, but never experimentally demonstrated before.;We have extended our analysis of gradients and their influence on growth by showing that the Fat tumor suppressor pathway activity in Drosophila is regulated by the gradients of the upstream modulators Dachsous (DS) and Four-jointed (FJ). This finding is exciting as aberrations in Fat pathway activity lead to tumorous overgrowths in both flies and mammals, and understanding how its activity is controlled is of critical interest. Furthermore, we have investigated a potential link between the DPP and the Fat signaling pathways. Our data suggest that DPP might regulate proliferation in the fly wing at least in part by establishing the gradients of expression of DS and FJ.