Theories of branching morphogenesis

04/07/2022 1:00 pm - 2:26 pm

Abstract: The morphogenesis of branched tissues has been a subject of long-standing debate. Although much is known about the molecular pathways that control cell fate decisions, it remains unclear how macroscopic features of branched organs, including their size, network topology and spatial pattern are encoded. Based on large-scale reconstructions of the mouse mammary gland and kidney, we begin by showing that statistical features of the developing branched epithelium can be explained quantitatively by a local self-organizing principle based on a branching and annihilating random walk (BARW). In this model, renewing tip-localized progenitors drive a serial process of ductal elongation and stochastic tip bifurcation that terminates when active tips encounter maturing ducts. Then, based on reconstructions of the developing mouse salivary gland, we propose a generalisation of BARW model in which tips arrested through steric interaction with proximate ducts reactivate their branching programme as constraints become alleviated through the expansion of the underlying mesenchyme. This inflationary branching-arresting random walk model offers a more general paradigm for branching morphogenesis when the ductal epithelium grows cooperatively with the tissue into which it expands.