Figure 2.

MST1/2 and YAP expression during normal pancreas development. MST1/2 mRNA levels are highest during the embryonic phase and lowest at birth. MST1 mRNA expression reappears at postnatal day 7 and later stages. Phosphorylated MST1/2 expression (active Hippo signaling) is broadly detectable in adult human pancreas, and islet cells display strong expression of phosphorylated MST1/2. YAP is broadly expressed throughout the pancreatic and duodenal E12.5 mouse pancreas (primary transition), but then gradually becomes restricted to prospective ductal and acinar regions at E16.5 (secondary transition). In the adult mouse pancreas, YAP expression is markedly decreased and the strong expression is largely confined to ductal and terminal-duct centroacinar cells, unlike in the embryonic pancreas. In pancreatic MST1/2 double knockout (DKO) mice, nuclear YAP staining is observed in the “trunk” regions during the embryonic phase, but is almost undetectable at birth. Thereafter, YAP expression is weak and confined mainly to the ductal compartment at birth and later postnatal stages. In pancreatic MST1/2 DKO mice, abundant YAP expression was observed in abnormally numerous duct-like structures during the postnatal phase. YAP remains undetectable within endocrine cells even in the absence of MST1/2. Pancreatic MST1/2 DKO mice show the histologic features of acute pancreatitis and decreased size (an approximately 2-fold decrease in pancreas mass).