Fig. 5

Bmp2b Overexpression Causes a Pancreatic-to-Liver Fate Switch

(A–F) Dorsal views of hhex (A–C) and pdx1 (D–F) expression at 44 hpf, comparing control (A and D) and Bmp2b-overexpressing embryos (heat shock applied at the 8 [B and E] or 14 [C and F] somite stage). The liver and the dorsal pancreatic bud are marked by black brackets and white dotted lines, respectively. hhex is expressed in the liver and dorsal pancreatic bud (A). pdx1 is expressed in the developing gut, including the pancreas and intestine, but not in the liver (D). When bmp2b expression was induced at the 8 somite stage, endodermal hhex expression was greatly expanded (B) while pdx1 expression was reduced (E). When bmp2b expression was induced at the 14 somite stage, endodermal hhex expression was only slightly expanded (C), while pdx1 expression was maintained (F).

(G–I) Ventral views of confocal projection images showing Prox1 (red), Islet1 (white), and Tg(ptf1a:GFP)^jh1 (green) expression at 50 hpf, comparing control (G) and Bmp2b-overexpressing embryos (heat shock applied at the 8 [H] or 14 [I] somite stage). Prox1 is highly expressed in the liver as well as in the ventral pancreas, which is also marked by Tg(ptf1a:GFP)^jh1 expression (arrows) (G). Islet1 is expressed in the mesenchymal cells surrounding the hepatopancreatic duct as well as in the pancreatic endocrine cells. Prox1 expression was greatly expanded when bmp2b expression was induced at the 8 somite stage (H), while Tg(ptf1a:GFP)^jh1 expression was completely lost. When bmp2b expression was induced at the 14 somite stage (I), Prox1 expression was only slightly expanded, while the ventral pancreas was specified and exhibited Tg(ptf1a:GFP)^jh1 expression (arrows).

(J) Schematic diagram of lineage tracing experiment. A single L1 cell at the level of somite 2, which normally gives rise to the pancreas and intestine, was uncaged (red boxes).

(K and L) Confocal projections of Tg(sox17:GFP)^s870 embryos at 50 hpf stained for GFP (green), Prox1 (blue), and uncaged-fluorescein (red). In control embryos (K), L1 cells gave rise to pancreas and intestine (arrows), but not to liver. In embryos induced to overexpress bmp2b at the 8 somite stage (L), L1 cells contributed to the liver (arrows), as marked by Prox1 (blue).