MORPHOGEN · Morphogenetic growth control by time derivatives of signaling

How do naïve cells in a developing tissue know when to divide and when to stop dividing when the tissue reaches its final size? How do they acquire information about their position to generate morphological patterns? Morphogen gradients have been shown to control pattern formation and growth. While the mechanisms of patterning are starting to be understood, the mechanism of growth by morphogens is not yet deciphered.In a few recent reports, we studied the biophysics and cell biology of the Dpp morphogen gradient during growth of Drosophila imaginal discs. We showed that the Dpp gradient expands and scales with the size of the growing tissue. Scaling occurs by the regulation of Dpp lysosomal degradation as a function of tissue size. We also showed that any cell in the developing tissue (no matter the developmental stage, the position of the cell in the gradient or the imaginal disc considered) divides when it sees an increase of Dpp signaling by α=50% from the beginning of the cell cycle. The proliferation rate g of cells is proportional to the relative time derivative of signaling (i.e. C ̇/C, the time derivative of Dpp signaling level C ̇ (Cdot) normalized to the actual signaling level C): g=(ln2/α)*(Cdot/C). We will study the molecular cell-biology of growth control by morphogens in an interdisciplinary combination of physical theory, biophysics and biochemistry in the context of development.