β-Catenin is critical for early postnatal liver growth

Udayan Apte, Gang Zeng, Michael D. Thompson, Peggy Muller, Amanda Micsenyi, Benjamin Cieply, Klaus H. Kaestner, Satdarshan P.S. Monga

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

The Wnt/β-catenin pathway plays an important role in embryonic liver development, morphogenesis, and organogenesis. Here, we report on the activation of β-catenin during early postnatal liver growth. Modulation of β-catenin expression was studied in CD-1 mice livers over a time course of 0 to 30 postnatal days (PD) and 3 mo. Increases in total and active β-catenin were observed in developing livers from PD 5 to 20. A concomitant increase in the β-catenin-transcription factor (TCF) complex along with nuclear and cytoplasmic β-catenin was also evident, which coincided with ongoing hepatocyte proliferation by PCNA immunohistochemistry. This activation of β-catenin was multifactorial, including cyclical inhibition of glycogen synthase kinase-3β, suppression of casein kinase-IIα, and a transient increase in β-catenin gene expression. Coprecipitation experiments revealed the formation of the β-catenin-cadherin complex at PD 5, whereas adequate β-catenin-c-Met complex at the hepatocyte membrane did not form until PD 20, which might be contributing to the free β-catenin pool during early postnatal growth. Furthermore, β-catenin liver-specific knockout mice exhibited smaller livers at PD 30, secondary to diminished hepatocyte proliferation. These data indicate that the activation of β-catenin is critical for early postnatal liver growth and development.

Original languageEnglish
Pages (from-to)G1578-G1585
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume292
Issue number6
DOIs
StatePublished - Jun 2007

Keywords

  • Casein kinase IIα
  • Glycogen synthase kinase-3β
  • Hepatocyte proliferation
  • Met
  • Transcription factor

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