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

De Langhe SP, Carraro G, Tefft D, Li C, Xu X, Chai Y, Minoo P, Hajihosseini MK, Drouin J, Kaartinen V, Bellusci S - PLoS ONE (2008)

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

View Article: PubMed Central - PubMed

Affiliation: 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.

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Related in: MedlinePlus

Decreased branching, partial right isomerization and epithelial proximalization in CKO lungs.(a–d) β-gal staining of Dermo1Cre/+/Rosa26R WT lungs at E11.5 and E13.5 reports Cre recombination activity in the mesenchyme of the embryonic lung. (a–b) Whole mount pictures of β-gal staining. (c) Vibratome section through E13.5 lung. (d) Paraffin section through E13.5 β-gal stained lung and counterstained with eosin. (e–h) (e) E12.5 WT and (f) CKO lungs which show decreased branching. (g) E14.5 WT lung and (h) CKO lung which shows partial right isomerization, astereotypic branching and a grape like structure, and absence of trachea. (i–j) H&E staining of sections through the left lobe of (i) E14.5 WT and (j) CKO lungs. Left lobe of CKO lung features proximalized airways and partial lobular septation. (k–l) Immunostaining for β-catenin on sections of (k) E14.5 WT and (l) CKO lungs show a mosaic deletion of β-catenin throughout the lung mesenchyme.
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pone-0001516-g001: Decreased branching, partial right isomerization and epithelial proximalization in CKO lungs.(a–d) β-gal staining of Dermo1Cre/+/Rosa26R WT lungs at E11.5 and E13.5 reports Cre recombination activity in the mesenchyme of the embryonic lung. (a–b) Whole mount pictures of β-gal staining. (c) Vibratome section through E13.5 lung. (d) Paraffin section through E13.5 β-gal stained lung and counterstained with eosin. (e–h) (e) E12.5 WT and (f) CKO lungs which show decreased branching. (g) E14.5 WT lung and (h) CKO lung which shows partial right isomerization, astereotypic branching and a grape like structure, and absence of trachea. (i–j) H&E staining of sections through the left lobe of (i) E14.5 WT and (j) CKO lungs. Left lobe of CKO lung features proximalized airways and partial lobular septation. (k–l) Immunostaining for β-catenin on sections of (k) E14.5 WT and (l) CKO lungs show a mosaic deletion of β-catenin throughout the lung mesenchyme.

Mentions: To monitor the onset and pattern of Cre activity in Dermo1Cre/+ lungs, we crossed the Dermo1Cre/+ mice [23] with Rosa26R reporter mice [24] and found a strong Cre-activity detectable in the mesenchyme surrounding the trachea and primary bronchi illustrated at E11.5 (Fig. 1a) and E13.5. This activity is detectable throughout the developing mesenchyme but not in the epithelium (Fig. 1b–d).


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

De Langhe SP, Carraro G, Tefft D, Li C, Xu X, Chai Y, Minoo P, Hajihosseini MK, Drouin J, Kaartinen V, Bellusci S - PLoS ONE (2008)

Decreased branching, partial right isomerization and epithelial proximalization in CKO lungs.(a–d) β-gal staining of Dermo1Cre/+/Rosa26R WT lungs at E11.5 and E13.5 reports Cre recombination activity in the mesenchyme of the embryonic lung. (a–b) Whole mount pictures of β-gal staining. (c) Vibratome section through E13.5 lung. (d) Paraffin section through E13.5 β-gal stained lung and counterstained with eosin. (e–h) (e) E12.5 WT and (f) CKO lungs which show decreased branching. (g) E14.5 WT lung and (h) CKO lung which shows partial right isomerization, astereotypic branching and a grape like structure, and absence of trachea. (i–j) H&E staining of sections through the left lobe of (i) E14.5 WT and (j) CKO lungs. Left lobe of CKO lung features proximalized airways and partial lobular septation. (k–l) Immunostaining for β-catenin on sections of (k) E14.5 WT and (l) CKO lungs show a mosaic deletion of β-catenin throughout the lung mesenchyme.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211394&req=5

pone-0001516-g001: Decreased branching, partial right isomerization and epithelial proximalization in CKO lungs.(a–d) β-gal staining of Dermo1Cre/+/Rosa26R WT lungs at E11.5 and E13.5 reports Cre recombination activity in the mesenchyme of the embryonic lung. (a–b) Whole mount pictures of β-gal staining. (c) Vibratome section through E13.5 lung. (d) Paraffin section through E13.5 β-gal stained lung and counterstained with eosin. (e–h) (e) E12.5 WT and (f) CKO lungs which show decreased branching. (g) E14.5 WT lung and (h) CKO lung which shows partial right isomerization, astereotypic branching and a grape like structure, and absence of trachea. (i–j) H&E staining of sections through the left lobe of (i) E14.5 WT and (j) CKO lungs. Left lobe of CKO lung features proximalized airways and partial lobular septation. (k–l) Immunostaining for β-catenin on sections of (k) E14.5 WT and (l) CKO lungs show a mosaic deletion of β-catenin throughout the lung mesenchyme.
Mentions: To monitor the onset and pattern of Cre activity in Dermo1Cre/+ lungs, we crossed the Dermo1Cre/+ mice [23] with Rosa26R reporter mice [24] and found a strong Cre-activity detectable in the mesenchyme surrounding the trachea and primary bronchi illustrated at E11.5 (Fig. 1a) and E13.5. This activity is detectable throughout the developing mesenchyme but not in the epithelium (Fig. 1b–d).

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

View Article: PubMed Central - PubMed

Affiliation: 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.

Show MeSH
Related in: MedlinePlus