MORPHOGRAD · Biophysical study of the coupling between cell proliferation and morphogen gradients

As well as controlling patterning, morphogens such as the Drosophila BMP homolog Decapentaplegic (Dpp) also regulate growth during development, but how they do so remains largely unclear. One privileged hypothesis, called the steepness hypothesis, suggests that cells in a tissue read spatial differences in the morphogen gradient and divide accordingly. However, the host lab recently discovered a novel mechanism by which the Dpp gradient controls growth: in the Drosophila wing disc, cells are able to read temporal differences in the Dpp gradient and regulate their cell cycle accordingly. More precisely, cells divide when their Dpp signalling level has increased by a constant percentage alpha since the start of their current cell cycle.Using biophysical methods, I will expand this work and study the molecular mechanisms coupling proliferation control with temporal changes in the Dpp gradient. I will generate cell cycle biosensors in order to monitor cell cycle parameters and their evolution throughout wing development, using fixed samples but also thanks to live imaging. I will also analyse the cell cycle and Dpp gradient characteristics in different tumourigenic conditions, in the hope to uncover general principles governing tumour formation. Finally, as several interactions have been uncovered between Dpp signalling and the tumour suppressor Hippo pathway, I will assess thanks to cell culture as well as in vivo assays whether the Hippo pathway could mediate the continued sensitivity of cells to the temporal Dpp signalling increase throughout development.