Schematic of Notch-responsive progenitors. In wild-type embryos (top), an early pancreatic progenitor (yellow) gives rise to early endocrine cells (green) as well as progenitors for late endocrine cells (white) located in the extrapancreatic duct (EPD) and pancreatic tail. Notch signaling maintains these latent progenitors in an undifferentiated state. Inhibition of Notch signaling by treatment with N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) (center) activates differentiation of the latent progenitors, leading to new endocrine cell formation in the principal islet and pancreatic tail (red arrows). In pdx1 morphants (bottom), early endocrine specification occurs but Notch-responsive progenitors for late endocrine cells are absent or hindered in differentiation, which can be demonstrated by treatment with DAPT.