beta-Catenin is not necessary for maintenance or repair of the bronchiolar epithelium.
Signaling by Wnt/beta-catenin regulates self-renewal of tissue stem cells in the gut and, when activated in the embryonic bronchiolar epithelium, leads to stem cell expansion. We have used transgenic and cell type-specific knockout strategies to determine roles for beta-catenin-regulated gene expression in normal maintenance and repair of the bronchiolar epithelium. Analysis of TOPGal transgene activity detected beta-catenin signaling in the steady-state and repairing bronchiolar epithelium. However, the broad distribution and phenotype of signaling cells precluded establishment of a clear role for beta-catenin in the normal or repairing state. Necessity of beta-catenin signaling was tested through Cre-mediated deletion of Catnb exons 2-6 in airway epithelial cells. Functional knockout of beta-catenin had no impact on expression of Clara cell differentiation markers, mitotic index, or sensitivity of these cells to the Clara cell-specific toxicant, naphthalene. Repair of the naphthalene-injured airway proceeded with establishment of focal regions of beta-catenin-null epithelium. The size of regenerative epithelial units, mitotic index, and restoration of the ciliated cell population did not vary between wild-type and genetically modified mice. Thus, beta-catenin was not necessary for maintenance or efficient repair of the bronchiolar epithelium.
Zemke
Anna C
AC
Center for Lung Regeneration, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Teisanu
Roxana M
RM
Giangreco
Adam
A
Drake
Jeff A
JA
Brockway
Brian L
BL
Reynolds
Susan D
SD
Stripp
Barry R
BR
D000818:Animals; D055745:Bronchioles / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D019426:Integrases / Q000235:genetics; D007763:Lac Operon; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008940:Mitotic Index; D009281:Naphthalenes / Q000633:toxicity; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012038:Regeneration / Q000187:drug effects / Q000235:genetics; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051820:TCF Transcription Factors / Q000235:genetics; D013997:Time Factors; D058118:Transcription Factor 7-Like 2 Protein; D014598:Uteroglobin / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
C495267:CTNNB1 protein, mouse; D009281:Naphthalenes; D012333:RNA, Messenger; C556390:Scgb1a1 protein, mouse; D051820:TCF Transcription Factors; C544895:Tcf7l2 protein, mouse; D058118:Transcription Factor 7-Like 2 Protein; D051176:beta Catenin; C031721:naphthalene; D014598:Uteroglobin; C045073:Cre recombinase; D019426:Integrases