Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
J Biol. 2004;3(3):11. Epub 2004 Jun 8.

Hyperactive Wnt signaling changes the developmental potential of embryonic lung endoderm.

Author information

  • 1Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA. t.okubo@cellbio.duke.edu

Abstract

BACKGROUND:

Studies in many model systems have shown that canonical signaling through the pathway downstream of ligands of the Wnt family can regulate multiple steps in organogenesis, including cell proliferation, differentiation, and lineage specification. In addition, misexpression of the Wnt-family member Wingless in Drosophila imaginal disc cells can lead to transdetermination of progenitors from one lineage to another. Conditional deletion of the beta-catenin component of the Wnt signaling pathway has indicated a role for Wnt signaling in mouse lung endoderm development. The full range of effects of this pathway, which includes the transcription factor Lef1, has not been explored, however.

RESULTS:

To explore this issue, we expressed a constitutively active beta-catenin-Lef1 fusion protein in transgenic embryos using a lung-endoderm-specific promoter from the surfactant protein C gene. Transgenic lungs appeared grossly normal, but internally they contained highly proliferative, cuboidal epithelium lacking fully differentiated lung cell types. Unexpectedly, microarray analysis and in situ hybridization revealed a mosaic of cells expressing marker genes characteristic of intestinal Paneth and goblet cells and other non-lung secretory cell types. In addition, there was strong ectopic expression of genes such as Cdx1 and Atoh1 that normally regulate gut development and early allocation of cells to intestinal secretory lineages.

CONCLUSIONS:

Our results show that hyperactive Wnt signaling in lung progenitors expressing a lung-specific gene can induce a dramatic switch in lineage commitment and the generation of intestinal cell types. We discuss the relevance of our findings to the poorly understood pathological condition of intestinal metaplasia in humans.

PMID:
15186480
[PubMed - indexed for MEDLINE]
PMCID:
PMC469027
Free PMC Article

Images from this publication.See all images (7)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for BioMed Central Icon for PubMed Central
    Loading ...
    Write to the Help Desk