An archetypal mechanism for branching organogenesis

Branched structures are ubiquitous in nature, both in living and non-living systems. While the functional benefits of branching organogenesis are straightforward, the developmental mechanisms leading to the repeated branching of epithelia in surrounding mesoderm remain unclear. Both molecular and physical aspects of growth control seem to play a critical role in shape emergence and maintenance. On the molecular side, the existence of a gradient of growth-promoting ligand between epithelial tips and distal mesenchyme seems to be common to branched organs. On the physical side, the branching process seems to require a mechanism of real-time adaptation to local geometry, as suggested by the self-avoiding nature of branching events. In this paper, we investigate the outcomes of a general three-dimensional growth model, in which epithelial growth is implemented as a function of ligand income, while the mesenchyme is considered as a proliferating viscous medium. Our results suggest that the existence of a gradient of growth-promoting ligand between distal and proximal mesenchyme implies a growth instability of the epithelial sheet, resulting in spontaneous self-avoiding branching morphogenesis. While the general nature of the model prevents one from fitting the development of specific organs, it suggests that few ingredients are actually required to achieve branching organogenesis.