Pancreas morphogenesis: Branching in and then out

The pancreas of adult mammals displays a branched structure which transports digestive enzymes produced in the distal acini through a tree-like network of ducts into the duodenum. In contrast to several other branched organs, its branching patterns are not stereotypic. Moreover, the branches do not grow from dichotomic splitting of an initial stem but rather from the formation of microlumen in a mass of cells. These lumen progressively assemble into a hyperconnected network that refines into a tree by the time of birth. We review the cell remodeling events and the molecular mechanisms governing pancreas branching, as well as the role of the surrounding tissues in this process. Furthermore, we draw parallels with other branched organs such as the salivary and mammary gland.