[HTML][HTML] Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by β-catenin signaling

SP De Langhe, G Carraro, D Tefft, C Li, X Xu, Y Chai… - PloS one, 2008 - journals.plos.org
SP De Langhe, G Carraro, D Tefft, C Li, X Xu, Y Chai, P Minoo, MK Hajihosseini, J Drouin…
PloS one, 2008journals.plos.org
Background The role of ฿-catenin signaling in mesodermal lineage formation and
differentiation has been elusive. Methodology To define the role of ฿-catenin signaling in
these processes, we used a Dermo1 (Twist2) Cre/+ line to target a floxed β-catenin allele,
throughout the embryonic mesenchyme. Strikingly, the Dermo1Cre/+; β-cateninf/−
conditional Knock Out embryos largely phenocopy Pitx1−/−/Pitx2−/− double knockout
embryos, suggesting that ฿-catenin signaling in the mesenchyme depends mostly on the …
Background
The role of ฿-catenin signaling in mesodermal lineage formation and differentiation has been elusive.
Methodology
To define the role of ฿-catenin signaling in these processes, we used a Dermo1(Twist2)Cre/+ line to target a floxed β-catenin allele, throughout the embryonic mesenchyme. Strikingly, the Dermo1Cre/+; β-cateninf/− conditional Knock Out embryos largely phenocopy Pitx1−/−/Pitx2−/− double knockout embryos, suggesting that ฿-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 β-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 ฿-catenin and PITX, as important regulators of mesenchymal cell proliferation and differentiation.
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