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PLoS One. 2008 Jan 30;3(1):e1516. doi: 10.1371/journal.pone.0001516.

Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.

Author information

1
Developmental Biology Program, Department of Surgery, Saban Research Institute of Childrens Hospital Los Angeles, Los Angeles, California, USA.

Abstract

BACKGROUND:

The role of ss-catenin signaling in mesodermal lineage formation and differentiation has been elusive.

METHODOLOGY:

To define the role of ss-catenin signaling in these processes, we used a Dermo1(Twist2)(Cre/+) line to target a floxed beta-catenin allele, throughout the embryonic mesenchyme. Strikingly, the Dermo1(Cre/+); beta-catenin(f/-) conditional Knock Out embryos largely phenocopy Pitx1(-/-)/Pitx2(-/-) double knockout embryos, suggesting that ss-catenin signaling in the mesenchyme depends mostly on the PITX family of transcription factors. We have dissected this relationship further in the developing lungs and find that mesenchymal deletion of beta-catenin differentially affects two major mesenchymal lineages. The amplification but not differentiation of Fgf10-expressing parabronchial smooth muscle progenitor cells is drastically reduced. In the angioblast-endothelial lineage, however, only differentiation into mature endothelial cells is impaired.

CONCLUSION:

Taken together these findings reveal a hierarchy of gene activity involving ss-catenin and PITX, as important regulators of mesenchymal cell proliferation and differentiation.

PMID:
18231602
PMCID:
PMC2211394
DOI:
10.1371/journal.pone.0001516
[Indexed for MEDLINE]
Free PMC Article

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