Table 1 Summary of developmental WNT/β-catenin signaling, expression pattern, study models, and phenotypes

 WNT2

MS

Wnt2 knockout

1. Hypoplastic lungs with relatively normal airway development

2. Reduced proliferation of EP and MS lineage

3. Several signaling pathways and transcription factors for lung development were reduced

[27]

 WNT2b

MS

Wnt2b knockout

Viable and no discernable phenotype

[27]

 WNT2/2b

MS

Wnt2/2b double knockout

Complete lung agencies

[27]

 WNT4

MS

Wnt4 knockout

1. Lung hypoplasia and tracheal abnormalities

2. Reduced mesodermal proliferation in the lung bud

[30]

 WNT5a

MS, EP(E12)

Distal and proximal EP (E16)

Cells surrounding distal and proximal EP (E18)

Wnt5a knockout

Wnt5a-SPC transgenic

1. Larger lungs, foreshortened trachea, overexpansion of distal airways, thickened intersaccular interstituim (knockout)

2. Smaller lungs, reduced number of alveolar sacs with dilated alveoli, lobation abnormalities (transgenic)

[31]

[32]

 WNT7b

EP (E12.5 to E16.5) both in the distal and larger mainstem bronchial airways

Conditional knockout of Wnt7b in Sox2-expressed embryo

1. Hypoplastic lungs with normal patterning and cell differentiation

2. Proportionate decrease in the replication of epithelial and mesenchymal progenitors

[29]

 FZDI

MS

In situ hybridization

NA

[33]

 FZD2

EP (distal)

Conditional knockout of Frz2 in Shh-expressing cells

Formation of cysts in distal airways and defective branching morphogenesis

[35, 36]

 FZD4

MS

In situ hybridization

NA

[33]

 FZD7

MS

In situ hybridization

NA

[33]

 FZD8

EP

In situ hybridization

[34]

 FZD10

EP (distal)

Immunohistochemistry

NA

[33]

 LRP5

EP (upper airway), muscular component of large vessels

Lrp5 knockout

Impairment of alveolar and vascular formation in neonatal lungs due to the decrease of angiopoietin/Tie2 pathway

[33, 37]

 LRP6

EP (upper airway)

In situ hybridization

NA

[33]

 DKK-1

EP (distal)

In situ hybridization

Treatment of E11.5 lung explants by Dkk1 disrupts branching morphogenesis

[34]

 SFRP-1

MS, EP (distal)

Sfrp-1 knockout

Marked dilation of the alveolar duct with the loss of surrounding messenchymal component

[43]

 APC

MS

Conditional knockout of Apc in Tbx4-expressing mesenchymal cells

APC knockout fetus shows severe lung hemorrhage in E14.5 and dies in E15.5, with condensed mesenchymal cells around epithelial tubes in the lung.

[44, 45]

 β-catenin

EP, MS

1. Conditional knockout of β-catenin in SPC-expressing cells

2. Conditional knockout of β-catenin in Shh-expressing cells

3. Conditional knockout of β-catenin in Sox2-expressing cells

4. Conditional knockout of β-catenin in Demol-expressing mesenchymal cells

1. Multiple, enlarged, and elongated bronchiolar tubes with a lack of alveolar sacs (β-catenin-SPC knockout)

2. Absence of both trachea and lung due to the defect of Nkx2.1 expression (B-catenin-Shh knockout)

3. Defective bronchiolar epithelial cell differentiation and marked ectasis of the developing and adult airway (β-catenin-Sox2 knockout)

4. Shortened trachea and reduced branching morphogenesis. Defect of sub-mesothelial mesenchymal domain containing Fgf10-expressing progenitors.

[26, 28, 38–40]