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Fig. 8. Jagged-mediated Notch signaling may regulate a binary cell-fate decision of zebrafish hepatoblasts. (A-F,I) Histological sections through the liver of 5-dpf wild-type (A-C) and jagged 2/3 morphant (D-F,I) larvae processed for cytokeratin and P-glycoprotein IHC. (A) A Branching network of bile ducts is evident in this wild-type larva. (B) Section in A processed for histology with superimposed pseudocolored cytokeratin pattern (magenta). (D) Four hepatocyte rosettes (arrows) are shown in this section through the liver of a jagged 2/3 morphant larva. Weak cytokeratin expression is also present in endothelial cells lining sinusoids seen in cross-section (arrowheads). (E) Section in D processed for histology with superimposed pseudocolored cytokeratin pattern (magenta). These sections show cytokeratin within the apical region of rosette cells (arrow indicates one of the four rosettes identified in D) and in surrounding sinusoidal endothelial cells (arrowhead). Dashed lines outline individual hybrid cells in two hepatocyte rosettes. (C,F) Wild-type (C) and jagged 2/3 morphant (F) larvae processed for P-glycoprotein IHC. Individual canaliculi are seen in the liver of wild-type larvae. In morphants, the P-glycoprotein is clustered in the central region of rosettes (arrow points to middle rosette). Compared with wild type, there is much less P-glycoprotein staining in the morphant liver. (I) Section shown in F stained for histological analysis. Red asterisks identify the location of P-glycoprotein+ cells (F). (G,H) Electron micrographs through the liver of 5-dpf jagged 2/3 morphant larvae. Low-power view (G) shows rosette cells with apical canaliculi (c), best appreciated in a high power view (H). Ultrastructurally, cells comprising the rosettes (dashed line in G) resemble hepatocytes. However, cytokeratin, a biliary marker, is also located apically in these cells (D).





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