Abstract

Branching morphogenesis is a process whereby flat epithelial sheets develop into tree like tissues. This process is driven by tip-localised progenitors that need to balance cell proliferation with differentiation and epithelial patterning, but how epithelial progenitors coordinate their output and how these cellular dynamics translate into the large-scale architecture of branched epithelia?. In this talk, we will discuss a multi scale approach to answer these questions. Using the murine salivary glands as a model system and a combination of clonal linage tracing, single-cell analysis and 3d reconstructions, we will show that progenitors form a heterogeneous population that organises in a lineage hierarchy regulated by Notch and KRAS signalling. Moreover, we will show how that the large-scale organisation of the branching epithelium is consistent with a probabilistic model of tip-branching and delay, which is driven by the persistent expansion of the ductal network and surrounding tissue.