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Cellular and Molecular Life Sciences

, Volume 65, Issue 21, pp 3467–3480 | Cite as

Origin of pancreatic endocrine cells from biliary duct epithelium

  • D. Eberhard
  • D. Tosh
  • J. M. W. SlackEmail author
Research Article

Abstract.

We describe an explant culture system to study the formation of pancreatic-type endocrine cells by the biliary tract. In this model, β-cells and other endocrine cells appear in the biliary duct epithelium and their number increases. Evidence for an origin from the duct epithelium is threefold. Firstly, differentiating cells transiently co-express insulin and bind Dolichos lectin. Secondly, β-cells in cultures isolated from Alb-Cre-R26R-LacZ mice are β-galactosidase positive. Thirdly, co-culture of biliary epithelium and ROSA26 pancreatic buds shows that endocrine cells do not migrate from the pancreas. The expression of the pancreatic transcription factors Pdx1, HNF6 and Sox9 is widespread, as is Hes1, which represses endocrine development, while that of Ngn3, which is a proendocrine transcription factor, is transient, consistent with an early stage of endocrine cell differentiation. Nicotinamide will increase the number of β-cells formed, while EGF+LIF completely inhibits their formation.

Keywords.

Pancreas development liver development β-cells Pdx1 Hes1 Ngn3 extrahepatic biliary system gall bladder development 

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Supplementary material

ESM1 (MPG 1.10 MB)

ESM2 (MPG 4.29 MB)

ESM3 (MPG 1.10 MB)

18_2008_8427_MOESM4_ESM.tif (961 kb)
ESM4 (TIFF 960 kb)

Copyright information

© Birkhaueser 2008

Authors and Affiliations

  1. 1.Centre for Regenerative Medicine, Department of Biology & BiochemistryUniversity of BathBathUK
  2. 2.Stem Cell InstituteUniversity of MinnesotaMinneapolisUSA

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