Real time quantification reveals novel dynamic processes in pancreatic lumenal network establishment and remodeling

Abstract

During embryogenesis dynamic changes in tissue architecture transform primitive anlages to functional organs. Here we document in real time how pancreatic lumens are derived and transformed using a new apical-polarity mouse reporter. Our 4D imaging data reveals dynamic remodeling of apical proteins and lumens to primarily drive each stage of pancreatic duct development. Furthermore, we pinpoint two unique transitions during lumenogenesis. Contrary to current "de novo" models of polarity acquisition, we show that expansion and rearrangement of the pre-existing central primary lumen drives early network growth. We also document how the endocrine promoting niche - a "plexus" of interconnected ducts - is resolved. We show that an arborized network forms by gradual closing of ductal loops, rather than via pruning. 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.