Fig. 1
From: Vitamin A-retinoid signaling in pulmonary development and disease
Retinoid regulation of early lung development. a At the onset of lung development, mesodermal RA signaling suppresses Dkk1 to allow induction of Wnt pathway and inhibits Tgf-beta signaling to de-repress Fgf10 expression. Thus, RA coordinately controls proper Fgf10 levels to activate Fgf signaling to the foregut endoderm and form the lung primordium. RA regulation of Tgf-beta effects in endoderm has also been suggested. b During airway formation, mesodermal (mesenchymal) RA signaling restricts SM gene expression (Acta2, Myh11, Tagln) in distal lung, preventing ectopic and excessive SM differentiation while airways are branching. RA may potentially inhibit a key activator of SM transcription or induce a transcriptional repressor to control SM gene expression (diagram: myocardin, serum response factor, CArG DNA binding sites at SM gene promoters). Modified from Chen et al. [14, 15]