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Role of the Wnt/ B-Catenin Pathway in Liver Development and Zonation

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Role of the Wnt/ B-Catenin Pathway in Liver Development and Zonation University of Bath PHD Role of the Wnt/ -catenin Pathway in Liver Development and Zonation Shen Wen, Yeh Award date: 2012 Awarding institution: University of Bath Link to publication Alternative formats If you require this document in an alternative format, please contact: [email protected] General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Download date: 10. Oct. 2021 Role of the Wnt/ -catenin Pathway in Liver Development and Zonation YEH, SHENG-WEN A thesis submitted for the degree of Doctor of Philosophy University of Bath Department of Biology and Biochemistry September, 2012 COPYRIGHT Attention is drawn to the fact that copyright of this thesis rests with the author. A copy of this thesis has been supplied on condition that anyone who consults it is understood to recognise that its copyright rests with the author and that they must not copy it or use material from it except as permitted by law or with the consent of the author. This thesis may be made available for consultation within the University Library and may be photocopied or lent to other libraries for the purposes of consultation. ___________________________________________________________ CONTENT Content ................................................................................................................................................... 1 List of figures and tables ...................................................................................................................... 10 Acknowledgements .............................................................................................................................. 14 Abstract ................................................................................................................................................ 15 Abbreviations ....................................................................................................................................... 17 Chapter 1 General Introduction ........................................................................................................... 21 1.1 Liver development ................................................................................................................. 22 1.2 Liver zonation ........................................................................................................................ 28 1.3 Wnt/-catenin signalling pathway ......................................................................................... 34 1.4 Wnt/-catenin signalling in liver development ...................................................................... 38 1.4.1 The role of Wnt/-catenin pathway in liver zonation ................................................. 42 1.5 Transdifferentiation................................................................................................................ 45 1.5.1 The definition of transdifferentiation .......................................................................... 45 1 1.5.2 Transdifferentiation of pancreas to liver ..................................................................... 46 1.5.3 The Wnt pathway and hepatic transdifferentiation of pancreatic cells ....................... 52 1.6 Aims ....................................................................................................................................... 53 Chapter 2 Materials and Methods ........................................................................................................ 56 2.1 Materials ................................................................................................................................ 57 2.1.1 Mouse Lines ................................................................................................................ 57 2.1.2 General chemicals, fixatives and buffers .................................................................... 57 2.1.3 Cell culture medium, reagents and exogenous factors ................................................ 58 2.1.4 Markers for immunofluorescence cell staining ........................................................... 59 2.1.5 Primary and secondary antibodies used for staining tissue sections ........................... 60 2.1.6 Western blotting materials, reagents, primary and secondary antibodies ................... 61 2.1.7 RNA extraction, reverse transcription (RT) and polymerase chain reaction (PCR) reagents and experimental conditions .................................................................................. 62 2.1.8 Adenovirus (Ad) reagents, materials and kits ............................................................. 65 2 2.1.9 Other instruments ........................................................................................................ 66 2.2 Methods.................................................................................................................................. 67 2.2.1 Cell culture .................................................................................................................. 67 2.2.1.1 Cell culture ....................................................................................................... 67 2.2.1.2 Cell culture maintenance.................................................................................. 67 2.2.1.3 Cell storage and revival ................................................................................... 68 2.2.1.4 Inoculation of cells ........................................................................................... 68 2.2.2 Fractionation of liver tissue ........................................................................................ 68 2.2.3 Western blotting .......................................................................................................... 69 2.2.4 Semi-quantitative RT-PCR ......................................................................................... 70 2.2.5 Fluorescence microscopy and image processing ........................................................ 70 2.2.6 In situ hybridization .................................................................................................... 71 2.2.6.1 Mice and isolation of embryos ......................................................................... 71 2.2.6.2 RNA probe synthesis ....................................................................................... 73 3 2.2.6.3 Tissue preparation ............................................................................................ 74 2.2.6.4 In situ hybridization on sections ...................................................................... 74 2.2.7 Immunohistochemistry of mouse liver ....................................................................... 75 2.2.7.1 Tissue Fixation, Embedding, and Processing .................................................. 75 2.2.7.2 Immunohistochemical Analysis of Embryonic Mouse Liver .......................... 76 2.2.8 Embryonic mouse liver bud dissection ....................................................................... 77 2.2.9 Embryonic culture of mouse liver buds ...................................................................... 79 2.2.10 Adenoviral infections ................................................................................................ 79 2.2.10.1 Amplification of first-generation adenovirus ................................................. 79 2.2.10.2 Further adenovirus amplification and dialysis ............................................... 80 2.2.10.3 Rapid titre of adenovirus ................................................................................ 81 Chapter 3 Expression profiling of hepatocyte markers and Wnt ligands and receptors during embryonic liver development .............................................................................................................. 82 3.1 Background ............................................................................................................................ 83 4 3.2 Results .................................................................................................................................... 85 3.2.1 Expression of CPS and GS during development ........................................................ 85 3.2.2 Expression of -catenin during development ............................................................. 90 3.2.3 Expression of Wnt pathway components during liver development .......................... 93 3.2.3.1 Wnt4 ................................................................................................................. 93 3.2.3.2 Wnt5a ............................................................................................................... 93 3.2.3.3 Wnt5b ..............................................................................................................
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