The enzyme Carboxipeptidase A1 (Cpa1) is expressed in the multipotent progenitor cell population located at the tip of the E13.5 branching epithelium in control, Gata4flox/flox;Gata6flox/+;Pdx1-Cre, and Gata4flox/+;Gata6flox/flox;Pdx1-Cre mice (A–C, arrowheads). In stark contrast, Cpa1+ cells were not detected in the double-mutant pancreatic epithelium (D). The proendocrine markers Ngn3 (E–G) and Nk2.2 (I–K) were mainly expressed in the epithelial trunk of control, Gata4flox/flox;Gata6flox/+;Pdx1-Cre, and Gata4flox/+;Gata6flox/flox;Pdx1-Cre embryos at E13.5. On the contrary, endocrine differentiation is disrupted in the double-mutant embryos as the number of cells expressing Ngn3 (H) and Nkx2.2 (L) are reduced compared with littermate embryos. The pancreatic epithelium is outlined in white in H and L. Counterstaining with DAPI was performed to reveal nuclei. Scale bars: 50 μm.