From molecules to tissues and back: scaling and shaping morphogen gradients

How morphogen gradients are formed has been under debate since the term was first coined by Alan Turing. Can diffusion alone lead to the robust formation of morphogen gradients? Or are cell processes like transcytosis important to move molecules across tissues? In this work we develop a theoretical framework to establish how the combination of different processes at the molecular and cellular level can in principle lead to morphogen gradient formation and its scaling to tissue size. We use this framework together with a sequence of independent experimental assays to quantify the relative contribution of different processes to the formation of the Dpp gradient in the fly wing. For large discs we find that a combination of hindered diffusion and recycling of endocytosed molecules drive Dpp gradient fromation. By studying wing discs of different sizes, we show that the relative contribution of endocytosed molecules to Dpp transport becomes progressively more pronounced during growth. Furthermore, the contribution of recycled molecules is diminished when the extracellular factor Pentagone is impaired. Our findings suggest that Pentagone modulates the contribution of recycled molecules to the diffusing pool. I will discuss potential mechanisms through which Pentagone encodes information about tissue size and their evolution.Finally, I will present a framework that takes into account cell and tissue architecture to ask how morphogenesis may impact the transport of morphogen molecules and patterning.