Table 3.
Involvement of PCP in nonmalignant human lung disease
| Gene (human symbol) |
Role in PCP | Mouse mutant line | Viability | Lung phenotype | References |
|---|---|---|---|---|---|
| Vangl1 (VANGL1) | core PCP protein | Vangl1CKO | viable | misoriented airway cilia | Vladar et al. [60] |
| Vangl1Gt | viable | misoriented airway cilia | Vladar et al. [60] | ||
| Vangl2 (VANGL2) | core PCP protein | Vangl2 Lp | E18.5 lethal | hypoplastic lungs with fewer branches; thickened interstitial mesenchyme; defective sacculation | Yates et al. [21,36] |
| Vangl2 Lp | E18.5 lethal | misoriented airway cilia | Vladar et al. [60] | ||
| Vangl2Lp heterozygote | viable | airspace enlargement; tissue damage reminiscent of emphysema | Poobalasingam et al. [13] | ||
| Prickle2 (PRICKLE2) | core PCP protein | Prickle2 germline knockout | viable | misoriented airway cilia | Vladar et al. [12] |
| Celsr1 (CELSR1) | core PCP protein | Celsr1 Crsh | E18.5 lethal | hypoplastic lungs with fewer branches; thickened interstitial mesenchyme; defective sacculation | Yates et al. [21,36] |
| Flattop (CFAP126) | putative PCP effector | Fltp germline knockout | viable | ciliogenesis defect due to undocked basal bodies | Gegg et al. [69] |
| Fuzzy (FUZ) | putative PCP effector | Fuz Gt1(neo) | E18.5 lethal | hypoplastic lungs | Gray 2009 [81] |
| Ptk7 (PTK7) | putative noncanonical co-receptor | Chuzhoi | E18.5 lethal | hypoplastic lungs with fewer branches; thickened interstitial mesenchyme; defective sacculation | Paudyal et al. [39] |
| Wntless (WLS) | Wnt secretion regulator | WlsShhCre (epithelial deletion) | P0 lethal | hypoplastic lungs with fewer branches; thickened interstitial mesenchyme; disrupted pulmonary endothelial differentiation | Cornett et al. [45] |
| WlsDermo1Cre (mesenchymal deletion) | E14.5 lethal | lung abnormalities not observed at E14.5 | Cornett et al. [45] | ||
| Wnt4 (WNT4) | Wnt family ligand | Wnt4 germline knockout | E18.5 lethal | hypoplastic lungs; defective cartilage formation | Caprioli et al. [53] |
| Wnt5a (WNT5A) | Wnt family ligand | Wnt5a germline knockout | P0 lethal | short and wide trachea; abnormally branched distal airways; thickened interstitial mesenchyme; defective sacculation; endothelial cell and capillary disorganization | Li et al. [43] |
| SpC-Wnt5a (epithelial overexpression) | viable | reduced epithelial branching | Li et al. [46] | ||
| Wnt5aDermo1Cre (mesenchymal deletion) | not reported | abnormally polarized smooth muscle cells along trachea | Kishimoto et al. [59] | ||
| Wnt5aECKO (endothelial deletion) | viable | Fewer pulmonary microvessels with decreased muscularization and pericyte coverage | Yuan et al. [88] |