The homeobox transcription factor Cux1 coordinates postnatal epithelial developmental timing but is dispensable for lung organogenesis and regeneration
Lung epithelial progenitors use a complex network of known and predicted transcriptional regulators to influence early lung development. Here, we evaluate the function of one predicted regulator, Cux1, that we identified from transcriptional regulatory analysis of the SOX9+ distal lung progenitor network. We generated a new Cux1-floxed mouse model and created an epithelial-specific knockout of Cux1 using Shh-Cre (Cux1ShhCre-LOF). Postnatal Cux1ShhCre-LOF animals recapitulate key skin phenotypic features found in prior constitutive Cux1 knockout animals, confirming functionality of the new floxed model. Postnatal Cux1ShhCre-LOF mice displayed subtle alveolar simplification and a transient delay in alveologenesis without persistent lung phenotypes or alterations in lung epithelial cell allocation. Cux1ShhCre-LOF mice developed failure to thrive in their second and third weeks of life due to delayed ileal maturation, which similarly resolves by postnatal day 35. Finally, we challenged Cux