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Beta‐catenin is essential for normal liver development
Author(s) -
Tan Xinping,
Yuan Youzhong,
Monga Satdarshan P. S.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a630
Subject(s) - biology , wnt signaling pathway , embryogenesis , embryonic stem cell , catenin , andrology , proliferating cell nuclear antigen , beta catenin , carcinogenesis , apoptosis , microbiology and biotechnology , immunohistochemistry , embryo , immunology , medicine , cancer , biochemistry , genetics , signal transduction , gene
β‐Catenin is important in embryogenesis & carcinogenesis. β‐Catenin knockout (k.o.) has been embryonic lethal, precluding analysis of its tissue‐specific role in development, which is now feasible with the advent of cre‐lox approach. Previously, we have reported temporal expression & activation of β‐catenin during early liver development. Here, we utilized floxed β‐catenin mice (lox‐P sites flanking Ex2‐6) & FoxA3‐Cre transgenic mice to generate liver‐specific β‐catenin k.o. No viable pup carrying β‐catenin deletion in liver was observed suggesting prenatal loss. Liver development examination revealed lethality at embryonic day 17 (E17) to E19 stage. A significant decrease in β‐catenin was observed in endodermal‐derived hepatic epithelial cells in the liver after E12. There was a significant compromise in liver size (2–5 times) as compared to the control littermates beyond E14 stage. H&E showed decreased epithelial cells in the k.o. livers and was confirmed by decreased number of E‐cadherin (by 50%), α‐FP and β1‐integrin‐positive cells by FACS, IHC and WB. HSC from the k.o. livers were sorted and analyzed by colony‐forming cell unit (CFC) assay and revealed no intrinsic defect in hematopoiesis. The E‐cadherin+ cells from the same livers failed to propagate in cultures. In addition the morphology of remnant hepatocytes in k.o. livers at E17‐E19 stages was distinct and lacked polarity, differentiation and glycogen accumulation. Also, these hepatocytes showed diminished proliferation (PCNA) and survival (TUNEL). EM studies showed increased epithelial cell death as well. Thus β‐catenin is essential in normal liver morphogenesis and appears crucial for hepatocyte differentiation or maturation, expansion and survival, which are indispensable to survival.