Hhex regulates the specification and growth of the hepatopancreatic ductal system

Abstract

SUMMARYSignificant efforts have advanced our understanding of foregut-derived organ development; however, little is known about the molecular mechanisms that underlie the formation of the hepatopancreatic ductal (HPD) system. Here, we report a role for the homeodomain transcription factor Hhex in directing HPD progenitor specification in zebrafish. Loss of Hhex function results in impaired HPD system formation. We found that Hhex specifies a distinct population of HPD progenitors that gives rise to the cystic duct, common bile duct, and extra-pancreatic duct. Since hhex is not uniquely expressed in the HPD region but is also expressed in endothelial cells and the yolk syncytial layer (YSL), we tested the role of blood vessels as well as the YSL in HPD formation. We found that blood vessels are required for HPD patterning, but not for HPD progenitor specification. In addition, we found that Hhex is required in both the endoderm and the YSL for HPD development. Our results shed light on the mechanisms necessary to direct endodermal progenitors towards the HPD fate and also advance our understanding of HPD system formation.

Role of YAP1 Signaling in Biliary Development, Repair, and Disease

“…68 70 Activation of transcription factors including hematopoietically expressed homeobox protein (Hhex), Hnf6, and Hnf1β, along with BMP and FGF signals from the adjacent mesenchyme, has also been shown to play a critical role in EHBD formation. 67 71 72 Multiple mechanical signals regulated by Eph/Ephrin interactions regulate the formation of a continuous lumen from differentiating cholangiocytes. 73 Finally, there is some evidence that the Wnt and Hippo pathways contribute to EHBD formation, both within the biliary cells themselves and also from nearby hepatocytes.…”