Fig. 2: Pancreatic organogenesis in mice and the role of Hippo pathway in cell lineage determination. Ventral and dorsal pancreatic buds form a single organ by E12.5.

Following extensive branching, cellular differentiation, and migration, the pancreatic ductal epithelium gives rise to exocrine cells (green) and endocrine cells (blue and pink). The endocrine cells subsequently migrate into the surrounding mesenchyme, where they contribute to the formation of pancreatic islets. a Emergence of independent dorsal and ventral pancreatic primordia from the foregut endoderm at around E9.5. b During the primary stage of development, Hippo pathway suppression enables rapid proliferation of undifferentiated pancreatic progenitor cells, supporting the growth of dorsal and ventral buds. c Integration of dorsal and ventral buds into a single organ by E12.5 after elongation and gut rotation. d, e The onset of the secondary transition at E12.5 marks the compartmentalization of the pancreatic epithelium into trunk (duct/endocrine precursors) and tip (acinar precursors) domains, with the trunk containing bi-potent cells that initially differentiate into β- and α-cells between E13.0 and E15.0. f, g During late embryogenesis (E16.5–18.5), differentiated cells migrate and organize to form the mature pancreas, with PP cells emerging and endocrine cells moving from the center to the periphery near exocrine tissues.