Wnt7b stimulates embryonic lung growth by coordinately increasing the replication of epithelium and mesenchyme.
The effects of Wnt7b on lung development were examined using a conditional Wnt7b-null mouse. Wnt7b-null lungs are markedly hypoplastic, yet display largely normal patterning and cell differentiation. In contrast to findings in prior hypomorphic Wnt7b models, we find decreased replication of both developing epithelium and mesenchyme, without abnormalities of vascular smooth muscle development. We further demonstrate that Wnt7b signals to neighboring cells to activate both autocrine and paracrine canonical Wnt signaling cascades. In contrast to results from hypomorphic models, we show that Wnt7b modulates several important signaling pathways in the lung. Together, these cascades result in the coordinated proliferation of adjacent epithelial and mesenchymal cells to stimulate organ growth with few alterations in differentiation and patterning.
Rajagopal
Jayaraj
J
Department of Molecular and Cellular Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Carroll
Thomas J
TJ
Guseh
J Sawalla
JS
Bores
Sam A
SA
Blank
Leah J
LJ
Anderson
William J
WJ
Yu
Jing
J
Zhou
Qiao
Q
McMahon
Andrew P
AP
Melton
Douglas A
DA
D000818:Animals; D019898:Autocrine Communication; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000502:physiology*; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000002:abnormalities / Q000166:cytology / Q000196:embryology*; D008297:Male; D008648:Mesoderm / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000196:embryology; D019899:Paracrine Communication; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology*
D006023:Glycoproteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; C095937:Wnt7b protein, mouse