Abstract

The mechanisms that specify the complex organization of branched tissues has been the subject of long-standing debate. Although much is known about the molecular programmes that control the underlying cell fate decisions, it remains unclear how macroscopic features of branched organs, including their size, ductal network topology and spatial pattern are encoded. Based on large-scale three-dimensional reconstructions of the developing mouse mammary gland and kidney epithelium, we show that statistical features of branched epithelia can be explained quantitatively through a local self-organizing principle based on the branching and annihilating random walk (BARW). We discuss emergent features of the BARW model and its generalizations to different branching contexts, and we contrast its behaviour to more stereotypic branching programmes. Finally, we highlight how the problem of branching morphogenesis provides a vivid illustration of how concepts and approaches from non-equilibrium statistical theory and active matter physics may find impact in the realm of developmental biology.