Cyp26b1 is an essential regulator of distal airway epithelial differentiation during lung development

Edward Daniel, Haley R. Barlow, Gabrielle I. Sutton, Xiaowu Gu, Yadanar Htike, Mitzy A. Cowdin, Ondine Cleaver

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Proper organ development depends on coordinated communication between multiple cell types. Retinoic acid (RA) is an autocrine and paracrine signaling molecule essential for the development of most organs, including the lung. Despite extensive work detailing effects of RA deficiency in early lung morphogenesis, little is known about how RA regulates late gestational lung maturation. Here, we investigate the role of the RA catabolizing protein Cyp26b1 in the lung. Cyp26b1 is highly enriched in lung endothelial cells (ECs) throughout development. We find that loss of Cyp26b1 leads to reduction of alveolar type 1 cells, failure of alveolar inflation and early postnatal lethality in mouse. Furthermore, we observe expansion of distal epithelial progenitors, but no appreciable changes in proximal airways, ECs or stromal populations. Exogenous administration of RA during late gestation partially mimics these defects; however, transcriptional analyses comparing Cyp26b1-/- with RA-treated lungs reveal overlapping, but distinct, responses. These data suggest that defects observed in Cyp26b1-/- lungs are caused by both RA-dependent and RA-independent mechanisms. This work reports crucial cellular crosstalk during lung development involving Cyp26b1-expressing endothelium and identifies a novel RA modulator in lung development.

Original languageEnglish (US)
Article numberdev181560
JournalDevelopment (Cambridge)
Issue number4
StatePublished - 2020
Externally publishedYes


  • Cyp26b1
  • Endothelial cell
  • Epithelial cell
  • Epithelium
  • Lung
  • Mouse
  • Retinoic acid

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology


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