Different thresholds of Wnt-Frizzled 7 signaling coordinate proliferation, morphogenesis and fate of endoderm progenitor cells

Dev Biol. 2013 Jun 1;378(1):1-12. doi: 10.1016/j.ydbio.2013.02.024. Epub 2013 Apr 3.

Abstract

Wnt signaling has multiple dynamic roles during development of the gastrointestinal and respiratory systems. Differential Wnt signaling is thought to be a critical step in Xenopus endoderm patterning such that during late gastrula and early somite stages of embryogenesis, Wnt activity must be suppressed in the anterior to allow the specification of foregut progenitors. However, the foregut endoderm also expresses the Wnt-receptor Frizzled 7 (Fzd7) as well as several Wnt ligands suggesting that the current model may be too simple. In this study, we show that Fzd7 is required to transduce a low level of Wnt signaling that is essential to maintain foregut progenitors. Foregut-specific Fzd7-depletion from the Xenopus foregut resulted in liver and pancreas agenesis. Fzd7-depleted embryos failed to maintain the foregut progenitor marker hhex and exhibited decreased proliferation; in addition the foregut cells were enlarged with a randomized orientation. We show that in the foregut Fzd7 signals via both the Wnt/β-catenin and Wnt/JNK pathways and that different thresholds of Wnt-Fzd7 activity coordinate progenitor cell fate, proliferation and morphogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Body Patterning
  • Cell Lineage
  • Cell Proliferation
  • Endoderm / cytology*
  • Gene Expression Regulation, Developmental*
  • Homeodomain Proteins / metabolism
  • Intestines / embryology
  • MAP Kinase Kinase 4 / metabolism
  • Morphogenesis / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Stem Cells / cytology*
  • Transcription Factors / metabolism
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway*
  • Xenopus Proteins / metabolism*
  • Xenopus laevis
  • beta Catenin / metabolism

Substances

  • Fzd7 protein, Xenopus
  • Homeodomain Proteins
  • Receptors, G-Protein-Coupled
  • Transcription Factors
  • Wnt Proteins
  • Xenopus Proteins
  • beta Catenin
  • hhex protein, Xenopus
  • ventx2.1 protein, Xenopus
  • MAP Kinase Kinase 4