Real-time imaging reveals new mechanisms for pancreatic ductal establishment and remodeling

During embryogenesis, dynamic changes in tissue architecture transform primitive anlages to functional organs. Using a new apical-polarity mouse reporter, we document in real time how the pancreatic ductal system is derived and transformed, revealing that dynamic remodeling of apical proteins and lumens primarily drive each stage. Contrary to current "de novo" models of polarity acquisition, we show that expansion and rearrangement of the preexisting central primary lumen drives early pancreatic ductal network establishment. The resulting ductal plexus creates unique ECM rich niches for endocrinogenesis, which are subsequently remodeled into an arborized system by a new mechanism, which we term "loop closing." We furthermore demonstrate that inner lumenal rearrangements precede outer epithelial branching. These novel tissue dynamics provide a new framework within which cell and molecular signaling can be investigated to better understand the interplay between organ architecture and cell fate.