RA plays an essential role in dorsal pancreas specification. During gastrulation and early neurulation, the field in dorsal endoderm that gives rise to the presumptive dorsal pancreas is just underlying the dorsal mesoderm where the highest concentration of RA is generated. These RA signals can act to underly endoderm either directly, or indirectly via first activating unknown factors (Xs) in mesoderm, which then act on the endoderm for dorsal pancreas formation. As described in the text, Shh and Cyp26a1 expressed in more anterior dorsal endoderm block pancreas formation probably via inhibiting the RA signaling activity or directly degrading RA. Cdx4 expressed in the posterior dorsal endoderm helps to establish the posterior boundary of dorsal pancreas via antagonizing the RA signaling.