β-Catenin maintains lung epithelial progenitors after lung specification

• DOI: 10.1242/dev.160788
• Publication Date: 2018-02-14T01:10:55Z
• Authors: Edwin J. Ostrin; Danielle R. Little; Kamryn N. Gerner-...; Elizabeth A. Sumner; Ricardo Ríos-Corzo; Elizabeth Ambrosio; Samantha E. Holt; Nicolas Forcioli-...; Haruhiko Akiyama; Sam M. Hanash; Shioko Kimura; Sarah X. L Huang; Jichao Chen
• Keywords: Progenitor; Ectopic expression

The entire lung epithelium arises from SRY box 9 (SOX9)-expressing progenitors that form the respiratory tree and differentiate into airway alveolar cells. Despite progress in understanding their initial specification within embryonic foregut, how these are subsequently maintained is less clear. Using inducible, progenitor-specific genetic mosaic mouse models, we showed β-catenin (CTNNB1) maintains by promoting a hierarchical progenitor gene signature, suppressing gastrointestinal (GI) genes, regulating NK2 homeobox 1 (NKX2.1) 2 (SOX2) developmental stage-dependent manner. At early, but not later, stage post-lung specification, CTNNB1 cell-autonomously normal NKX2.1 expression levels suppressed ectopic SOX2 expression. Genetic epistasis analyses revealed required for fibroblast growth factor (Fgf)/Kirsten rat sarcoma viral oncogene homolog (Kras)-mediated promotion of progenitors. In silico screening Eurexpress translating ribosome affinity purification (TRAP)-RNAseq identified subset which depends on CTNNB1. Wnt signaling also GI genes cultured human derived stem