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Biophysical study of the coupling between cell proliferation and morphogen gradients

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Cell growth in embryos

In a breakthrough that could lead to new cancer therapies, scientists have discovered how organs in developing embryos know when to stop growing.

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When cells divide in a developing embryo, they need to know which tissues to develop into and where and how large they should grow. This is achieved by substances called morphogens, which control where different cell types are found within tissues. Morphogens do this by diffusing through developing tissues into concentration gradients that tell cells when to start and stop dividing. At defined morphogen concentrations, specific genes are turned on or off. This results in cells developing into the correct type and leading to different tissues and organs in the developed embryo. While scientists know how morphogens subdivide tissues into patterns of distinct cell types, they know little about how morphogens control tissue growth. The EU-funded MORPHOGRAD (Biophysical study of the coupling between cell proliferation and morphogen gradients) project studied fruit flies to determine how a morphogen controls growth of the fly's wing disc. Cells in the embryonic fly's wing divide when they perceive a 50 % increase in the concentration of a morphogen called Decapentaplegic (Dpp). To find how cells sense this, researchers looked at a biochemical pathway called Hippo. This pathway controls cell proliferation by inhibiting growth when cells come into contact with each other. After confirming that Dpp influences target genes in the Hippo pathway in different ways, researchers interfered with the pathway in the fruit fly's embryonic wing disc. By looking at how wing discs grew after this disruption, MORPHOGRAD discovered two ways in which Hippo controls organ sizes. Firstly, Hippo-deficient cells divided for a longer time than normal cells, although the rate of cell division stayed the same. Secondly, Hippo-deficient cells started to divide upon sensing a smaller increase in Dpp concentration than in normal cells. This resulted in cell overgrowth, a hallmark of tumours. Apart from demonstrating how cell growth is regulated in developing embryos, MORPHOGRAD's results may be valuable for therapies to repress tumour growth.


Cell growth, embryos, morphogens, MORPHOGRAD, cell proliferation, decapentaplegic

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