Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
BACKGROUND
The role of ss-catenin signaling in mesodermal lineage formation and differentiation has been elusive.


METHODS
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.


CONCLUSIONS
Taken together these findings reveal a hierarchy of gene activity involving ss-catenin and PITX, as important regulators of mesenchymal cell proliferation and differentiation.
De Langhe
Stijn P
SP
Developmental Biology Program, Department of Surgery, Saban Research Institute of Childrens Hospital Los Angeles, Los Angeles, California, USA.
Carraro
Gianni
G
Tefft
Denise
D
Li
Changgong
C
Xu
Xin
X
Chai
Yang
Y
Minoo
Parviz
P
Hajihosseini
Mohammad K
MK
Drouin
Jacques
J
Kaartinen
Vesa
V
Bellusci
Savério
S
D000818:Animals; D015153:Blotting, Western; D019070:Cell Lineage; D049109:Cell Proliferation; D005346:Fibroblast Growth Factors / Q000378:metabolism; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D008168:Lung / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034741:RNA, Small Interfering; D015398:Signal Transduction; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D051176:beta Catenin; D005346:Fibroblast Growth Factors