beta-Catenin is required for specification of proximal/distal cell fate during lung morphogenesis.
The lungs are divided, both structurally and functionally, into two distinct components, the proximal airways, which conduct air, and the peripheral airways, which mediate gas exchange. The mechanisms that control the specification of these two structures during lung development are currently unknown. Here we show that beta-catenin signaling is required for the formation of the distal, but not the proximal, airways. When the gene for beta-catenin was conditionally excised in epithelial cells of the developing mouse lung prior to embryonic day 14.5, the proximal lung tubules grew and differentiated appropriately. The mice, however, died at birth because of respiratory failure. Analysis of the lungs by in situ hybridization and immunohistochemistry, using molecular markers of the epithelial and mesenchymal components of both proximal and peripheral airways, showed that the lungs were composed primarily of proximal airways. These observations establish, for the first time, both the sites and timing of specification of the proximal and peripheral airways in the developing lung, and that beta-catenin is one of the essential components of this specification.
Mucenski
Michael L
ML
Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA. michael.mucenski@cchmc.org
Wert
Susan E
SE
Nation
Jennifer M
JM
Loudy
David E
DE
Huelsken
Joerg
J
Birchmeier
Walter
W
Morrisey
Edward E
EE
Whitsett
Jeffrey A
JA
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002455:Cell Division; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D004318:Doxycycline / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D017353:Gene Deletion; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D019426:Integrases / Q000235:genetics; D008168:Lung / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D012333:RNA, Messenger; D015534:Trans-Activators; D014764:Viral Proteins; D051176:beta Catenin; C045073:Cre recombinase; D019426:Integrases; D004318:Doxycycline