TY - JOUR AB - Branching morphogenesis governs the formation of many organs such as lung, kidney, and the neurovascular system. Many studies have explored system-specific molecular and cellular regulatory mechanisms, as well as self-organizing rules underlying branching morphogenesis. However, in addition to local cues, branched tissue growth can also be influenced by global guidance. Here, we develop a theoretical framework for a stochastic self-organized branching process in the presence of external cues. Combining analytical theory with numerical simulations, we predict differential signatures of global vs. local regulatory mechanisms on the branching pattern, such as angle distributions, domain size, and space-filling efficiency. We find that branch alignment follows a generic scaling law determined by the strength of global guidance, while local interactions influence the tissue density but not its overall territory. Finally, using zebrafish innervation as a model system, we test these key features of the model experimentally. Our work thus provides quantitative predictions to disentangle the role of different types of cues in shaping branched structures across scales. AU - Ucar, Mehmet C AU - Kamenev, Dmitrii AU - Sunadome, Kazunori AU - Fachet, Dominik C AU - Lallemend, Francois AU - Adameyko, Igor AU - Hadjab, Saida AU - Hannezo, Edouard B ID - 10402 JF - Nature Communications TI - Theory of branching morphogenesis by local interactions and global guidance VL - 12 ER -