Table 1.
Summary of retinoic acid components, crosstalk, and knockouts during lung development.
| Lung Developmental Phase | RA Pathway Machinery | RA Pathway Targets | Knockouts with Lung Phenotype | References |
|---|---|---|---|---|
| Embryonic |
cyp26 raldh2 RARα, β, γ |
fgf10, FGFR2 WNT, wnt2/2b TGFβ HH bmp4 nkx2.1 |
raldh2−/− (lung agenesis) |
[40,41,42,43,44,45,46,47] |
| Pseudoglandular |
stra6 crbp raldh1, 2, 3 cyp26 rarα1, α2, β, γ coup-tfII |
fgf10, fgfr2 shh bmp4 foxa2 tgfβ2, β3 cftr hoxa2, a5, b5, b6 HOXB5 acta myh11 sox2, sox9, id2 meis2 crbpI raldh1 rarβ, RARα, β, γ |
rdh10−/− (absence of lung, primary lung bud growth arrested and branching impaired) raldh2−/− (hypoplastic lungs, defective growth and branching) rarαβ2−/− (lung agenesis and hypoplasia, absence of lung budding, altered branching) |
[16,41,43,49,50,51,52,53,54,55,56,57,58,62,64,69,70,71] |
| Canalicular | RARα | - | - | [84] |
| Saccular | rarα, β, γ | - | - | [84,88] |
| Alveolar | CRBPI, II CRABP RALDH1, 2 RARα, β, γ RXR |
VEGFA FGF signaling SPA, B, C, spa YAP TNF-α, TNFR1 IL6, IL6ST |
rarα−/− (↓ alveolar number and surface area) rarβ−/− (early & faster septation; ↓ surface area) rarγ−/− (↓ elastic tissue, ↓ alveoli number, ↑ distance between the alveolar walls) rxrα−/− (embryonic lethality) rarγ−/−, rxrα+/− (↓ elastic tissue at the alveolar septa) |
[88,94,97,104,107,108,109,110,111,112,123,126,127,130,134] |
↓, decrease; ↑, increase.