Wnt9a secreted from the walls of hepatic sinusoids is essential for morphogenesis, proliferation, and glycogen accumulation of chick hepatic epithelium

Ken Matsumoto, Rika Miki, Mizuho Nakayama, Norifumi Tatsumi, Yuji Yokouchi

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)

Abstract

Hepatic epithelial morphogenesis, including hepatoblast migration and proliferation in the septum transversum, requires the interaction of hepatic epithelium with the embryonic sinusoidal wall. No factors that mediate this interaction have yet been identified. As the β-catenin pathway is active in hepatoblast proliferation, then Wnt ligands might activate the canonical Wnt pathway during liver development. Here, we investigated the role of Wnts in mediating epithelial vessel interactions in the developing chick liver. We found that Wnt9a was specifically expressed in both endothelial and stellate cells of the embryonic sinusoidal wall. Induced overexpression of Wnt9a resulted in hepatomegaly with hyperplasia of the hepatocellular cords, and in hyperproliferation of hepatocytes. Knockdown of Wnt9a caused a reduction in liver size, with hypoplasia of hepatocellular cord branching, and hypoproliferation of hepatoblasts, and also inhibited glycogen accumulation at later developmental stages. Wnt9a promoted in vivo stabilization of β-catenin through binding with Frizzled 4, 7, and 9, and activated TOPflash reporter expression in vitro via Frizzled 7 and 9. Our results demonstrate that Wnt9a from the embryonic sinusoidal wall is required for the proper morphogenesis of chick hepatocellular cords, proliferation of hepatoblasts/hepatocytes, and glycogen accumulation in hepatocytes. Wnt9a signaling appears to be mediated by an Fzd7/9-β-catenin pathway.

Original languageEnglish
Pages (from-to)234-247
Number of pages14
JournalDevelopmental Biology
Volume319
Issue number2
DOIs
Publication statusPublished - 2008 Jul 15
Externally publishedYes

Keywords

  • Differentiation
  • Epithelial-vascular interaction
  • Hepatic cord
  • Hepatic epithelium
  • Hepatoblast
  • Hepatocellular cord
  • Hepatocyte
  • Hepatogenesis
  • Liver development
  • Morphogenesis
  • Proliferation
  • RNA interference
  • Short hairpin
  • Sinusoid
  • Stem cell
  • Wnt
  • β-catenin

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Wnt9a secreted from the walls of hepatic sinusoids is essential for morphogenesis, proliferation, and glycogen accumulation of chick hepatic epithelium'. Together they form a unique fingerprint.

Cite this