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Contrasting Expression of Canonical Wnt Signaling Reporters TOPGAL, BATGAL and Axin2LacZ during Murine Lung Development and Repair

By Denise Al Alam, Melissa Green, Reza Tabatabai Irani, Sara Parsa, Soula Danopoulos, Frederic G. Sala, Jonathan Branch, Elie El Agha, Caterina Tiozzo, Robert Voswinckel, Edwin C. Jesudason, David Warburton and Saverio Bellusci

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 Axin2LacZ. 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, Axin2LacZ 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). Axin2LacZ expression is increased in bronchial epithelium of injured lungs. Interestingly, both TOPGAL and Axin2LacZ 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

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:3153464
Provided by: PubMed Central

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Citations

  1. (2008). A Gata6-Wnt pathway required for epithelial stem cell development and airway regeneration.
  2. (2010). Activation of the WNT/{beta}-Catenin Pathway Attenuates Experimental Emphysema. Am J Respir Crit Care Med. Wnt Reporters
  3. (2009). beta-Catenin promotes respiratory progenitor identity in mouse foregut.
  4. (2010). Beta-catenin/Tcell factor signaling is activated during lung injury and promotes the survival and migration of alveolar epithelial cells.
  5. (1995). Cellular response in naphthalene-induced Clara cell injury and bronchiolar epithelial repair in mice.
  6. (2006). CKI, there’s more than one: casein kinase I family members in Wnt and Hedgehog signaling.
  7. (2005). Dickkopf-1 (DKK1) reveals that fibronectin is a major target of Wnt signaling in branching morphogenesis of the mouse embryonic lung.
  8. (2004). Essential role of BCL9-2 in the switch between beta-catenin’s adhesive and transcriptional functions.
  9. (1998). Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta.
  10. (2002). Gender differences in naphthalene metabolism and naphthalene-induced acute lung injury.
  11. (2004). Hyperactive Wnt signaling changes the developmental potential of embryonic lung endoderm.
  12. Lung organogenesis.
  13. (2003). Mapping Wnt/beta-catenin signaling during mouse development and in colorectal tumors.
  14. (1977). Morphology of a naphthalene-induced bronchiolar lesion.
  15. (1999). Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation.
  16. (2002). Negative feedback loop of Wnt signaling through upregulation of conductin/axin2 in colorectal and liver tumors.
  17. (1995). Plasticity of airway cell proliferation and gene expression after acute naphthalene injury.
  18. (2008). Rspondin 2 is required for normal laryngeal-tracheal, lung and limb morphogenesis.
  19. (2009). Towards an integrated view of Wnt signaling in development.
  20. (2010). Wnt proteins are self-renewal factors for mammary stem cells and promote their long-term expansion in culture.
  21. (2008). Wnt signaling in lung organogenesis.
  22. (2006). Wnt signaling: multiple pathways, multiple receptors, and multiple transcription factors.
  23. (1999). WNT targets. Repression and activation.
  24. (2009). Wnt/beta-catenin signaling: components, mechanisms, and diseases.