title: Contrasting expression of canonical Wnt signaling reporters TOPGAL, BATGAL and Axin2(LacZ) during murine lung development and repair.
abstract: Canonical WNT signaling plays multiple roles in lung organogenesis and repair by regulating early progenitor cell fates: investigation has been enhanced by canonical Wnt reporter mice, TOPGAL, BATGAL and Axin2(LacZ). Although widely used, it remains unclear whether these reporters convey the same information about canonical Wnt signaling. We therefore compared beta-galactosidase expression patterns in canonical Wnt signaling of these reporter mice in whole embryo versus isolated prenatal lungs. To determine if expression varied further during repair, we analyzed comparative pulmonary expression of beta-galactosidase after naphthalene injury. Our data show important differences between reporter mice. While TOPGAL and BATGAL lines demonstrate Wnt signaling well in early lung epithelium, BATGAL expression is markedly reduced in late embryonic and adult lungs. By contrast, Axin2(LacZ) expression is sustained in embryonic lung mesenchyme as well as epithelium. Three days into repair after naphthalene, BATGAL expression is induced in bronchial epithelium as well as TOPGAL expression (already strongly expressed without injury). Axin2(LacZ) expression is increased in bronchial epithelium of injured lungs. Interestingly, both TOPGAL and Axin2(LacZ) are up regulated in parabronchial smooth muscle cells during repair. Therefore the optimal choice of Wnt reporter line depends on whether up- or down-regulation of canonical Wnt signal reporting in either lung epithelium or mesenchyme is being compared.
authors.affiliation: Developmental Biology and Regenerative Medicine Program, Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, California, United States of America.
authors.forename: Denise
authors.initials: D
authors.lastname: Al Alam
authors.forename: Melissa
authors.initials: M
authors.lastname: Green
authors.forename: Reza
authors.initials: R
authors.lastname: Tabatabai Irani
authors.forename: Sara
authors.initials: S
authors.lastname: Parsa
authors.forename: Soula
authors.initials: S
authors.lastname: Danopoulos
authors.forename: Frederic G
authors.initials: FG
authors.lastname: Sala
authors.forename: Jonathan
authors.initials: J
authors.lastname: Branch
authors.forename: Elie
authors.initials: E
authors.lastname: El Agha
authors.forename: Caterina
authors.initials: C
authors.lastname: Tiozzo
authors.forename: Robert
authors.initials: R
authors.lastname: Voswinckel
authors.forename: Edwin C
authors.initials: EC
authors.lastname: Jesudason
authors.forename: David
authors.initials: D
authors.lastname: Warburton
authors.forename: Saverio
authors.initials: S
authors.lastname: Bellusci
mesh_terms: D000818:Animals; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D008168:Lung / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009281:Naphthalenes; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051820:TCF Transcription Factors / Q000235:genetics; D013997:Time Factors; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism*
chemical_list: D009281:Naphthalenes; D051820:TCF Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; C031721:naphthalene; D001616:beta-Galactosidase