Premium
Wnt/β‐Catenin pathway activation during normal postnatal liver growth and development
Author(s) -
Apte Udayan M,
Muller Peggy,
Awan Farrukh,
Otruba Wade,
Cieply Benjamin,
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.20.5.a1089-b
Subject(s) - wnt signaling pathway , catenin , hepatocyte , beta catenin , endocrinology , lrp6 , medicine , biology , axin2 , frizzled , gsk 3 , microbiology and biotechnology , glycogen synthase , signal transduction , chemistry , phosphorylation , biochemistry , in vitro
Wnt/β‐catenin pathway plays an important role in embryonic liver development. Here, we report the activation of β‐catenin during early postnatal liver development. Modulation of β‐catenin expression was studied in CD‐1 mice livers over a time course of 0 to 30 postnatal days (PD), 3 months and 8+ months. Extensive induction in total and active β‐catenin was observed at PD 5 to 20, along with its increased nuclear translocation that coincided with robust cell proliferation as demonstrated by PCNA analysis. This activation of β‐catenin was in part, via the canonical pathway secondary to glycogen synthase kinase 3‐β (GSK3β) inhibition. Coprecipitation studies revealed failure of β‐catenin‐c‐Met complex formation at the hepatocyte membrane till PD 20, complementing activation of β‐catenin, as this complex is a prominent β‐catenin regulatory pool at hepatocyte membrane, seen robustly in adult mice. β‐Catenin conditional knockouts showed smaller livers at PD 15 and 30, secondary to diminished hepatocyte proliferation and sustained hematopoiesis. Finally, mRNA for majority of Wnts, frizzled and Ctnnb1 was detected in PD 0 to 30 livers indicating the presence the main positive components of the Wnt/β‐catenin pathway during early postnatal development. Thus, activation of β‐catenin contributes to normal postnatal liver growth and development. (Supported by RSG‐03‐141‐01‐CNE and NIH ‐ 1RO1DK62277 to SPSM).