Although significant progress has been made toward understanding morphogen-mediated patterning in development, control of the size and shape of tissues via local and global signaling is poorly understood. In particular, little is known about how cell-cell interactions are involved in the control of tissue size. The Hippo pathway in the Drosophila wing disc involves cell-cell interactions via cadherins, which lead to modulation of Yorkie, a cotranscriptional factor that affects control of the cell cycle and growth, and studies involving over- and underexpression of components of this pathway reveal conditions that lead to tissue over- or undergrowth. Here, we develop a mathematical model of the Hippo pathway that can qualitatively explain these observations, made in both whole-disc mutants and mutant-clone experiments. We find that a number of nonintuitive experimental results can be explained by subtle changes in the balances between inputs to the Hippo pathway and suggest some predictions that can be tested experimentally. We also show that certain components of the pathway are polarized at the single-cell level, which replicates observations of planar cell polarity. Because the signal transduction and growth control pathways are highly conserved between Drosophila and mammalian systems, the model we formulate can be used as a framework to guide future experimental work on the Hippo pathway in both Drosophila and mammalian systems.
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This article was supported in part by National Institutes of Health grant number GM29123 .
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