Figure 7

Co-localization of transcripts for Atoh1 and SftpC in epithelial cells of transgenic lungs. Sections of E18.5 (a,b) wild-type or (c-h) transgenic lungs were viewed by either differential interference (DIC; a,c,g) or fluorescence (b,d-f,h) microscopy after hybridization with probes for SftpC (revealed by FITC in green) or Atoh1 (revealed by Cy3 in red). (b) Merged fluorescence images showing that in the wild-type lung SftpC is expressed in well-differentiated, rounded, type II cells. In contrast, no Atoh1 expression can be detected. (d) In the transgenic lung, SftpC, and by inference the transgene, is expressed in cuboidal epithelial cells. (e) Atoh1 is expressed in cuboidal epithelial cells. No expression is seen in mesothelial cells bordering the outer surface of the lung; the extrapulmonary region is marked by asterisks in (c-e). (f) Merged images showing co-expression of SftpC and Atoh1 in some cells. Some cells (arrows) show only Atoh1 expression. (h) Merged images of another region of the same transgenic lung show more extensive regions of the epithelium (arrows) in which only Atoh1 is expressed. Scale bar, 50 μm. (i) A model for the transdetermination of lung progenitor cells to intestinal lineages by hyperactive Wnt signaling. High levels of the Lef1/β-catenin fusion gene in lung progenitors directly induce expression of transcription factors such as Cdx1 and possibly Atoh1. These factors may also up-regulate each other. Cdx1 and/or Atoh1 promotes the respecification of the cells to intestinal secretory lineages; this would result in the down-regulation of the transgene.