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Table 1 Expression patterns of some lung signaling molecules, transcription factors, and other molecular factors and the phenotypes specified by their mutations, targeted inhibition, abrogation, blockage or underexpression

From: Comparative molecular developmental aspects of the mammalian- and the avian lungs, and the insectan tracheal system by branching morphogenesis: recent advances and future directions

Signaling molecule
  Gene name Expression site Phenotype References
FGF-18 Fibroblast growth factor-18 Mesenchyme Poor alveolization Usui et al. [135]
FGF-9 Fibroblast growth factor-9 Epithelium; mesothelium (future pleura) Little airway branching; mesenchymal hypoplasia Colvin et al. [136]; Yin et al. [17]
PDGF-a Platelet derived growth factor-a Epithelium Compromised myoblast and elastin formation; defective alveolization Bostrom et al. [137]; Buch et al. [138]
Notch-2/3 Notch gene homologue-2/3 Epithelium Defective alveolization Xu et al. [139]
FGFR-3/4 Fibroblast growth factor receptor-3/4 Epithelium; mesenchyme Deficient production of elastin; lacking alveolization Weinstein et al. [140]
BMP-4 Bone morphogenetic protein-4 Epithelium; Mesenchyme poor lung development with cystic terminal air spaces Bellusci et al. [141]; Weaver et al. [142]; Jang et al. [143]
FGFR-2b Fibroblast growth factor receptor-2b Epithelium Lung agenesis; flawed branching; poor epithelial cell differentiation De Moerlooze et al. [144]; Shu et al. [145]
FGF-10 Fibroblast growth factor-10 Mesenchyme Lung agenesis and different abnormalities Sekine et al. [146]; De Moerlooze et al. [144]; [147]
WNT-5a Wingless-related MMTV integration site-5A Mesenchyme; epithelium Excessive branching; tracheal deficiency Li et al. [148]
WNT-7b Wingless-related MMTV integration site-7B Epithelium Vascular scantiness; reduced mesenchymal proliferation Shu et al. [149]; Shi et al. [150]; Mucenski et al. [151]
TGF-3β Transforming growth factor-β3 Epithelium; mesothelium Anomalous airway branching; poor extent of alveolization Kaartinen et al. [152]; Shi et al. [153]
Shh Sonic hedgehog Epithelium Poor bronchial branching; hypoplastic lungs; tracheoesophangeal fistula Litingtung et al. [154]; Minoo et al. [155]
HIP-1 Hedgehog interacting protein-1 Mesenchyme Defective branching Chuang and McMahon [156]; Chuang et al. [26]
Catnnb-1 β- catenin Epithelium Impaired airway branching Mucenski et al.[151])
VEGF Vascular endothelial growth factor Epithelium; mesenchyme VEGF knockout have lethal phenotype; anormal vasculature Zeng et al. [157]; Miquerol et al. [158]; Kasahara et al. [159]
Nog Noggin Mesenchyme Lobation deficiencies Weaver et al. [142]
Transcription factors
FOXA-1/2 Forkhead box-A1/A2 Epithelium Hypoplastic lungs; defective branching; poor smooth muscle formation Wan et al. [160]
FOX-j1 Forkhead box-J1 Epithelium Deficiency of ciliated cells; left-right asymmetry Brody et al. [161]
FOX-F1a Forkhead box-F1a Mesenchyme Defective branching and lobation; tracheoesophangeal fistula Lim et al. [162]
HOX-A5 Homeobox-A5 Mesenchyme Tracheal occlusion; poor airway branching Aubin et al. [163]; Golpon et al. [164]
GATA-6 GATA-binding protein-6 Epithelium Diminished airway branching; defective sacculation Yang et al. [165]
Gli-2/3 GLI-Kruppel family member GLI-2/3 Mesenchyme Lung agenesis Motoyama et al. [166]; van Tuyl and Post [167]
Wnt-2/2b Wingless-related MMTV integration site-2/2b Mesenchyme Lung agenesis Harris-Johnson et al. [168]
NKX-2.1 (TTF-1) Nkx homeodomain/thyroid-specific transcription factor Epithelium Lung agenesis Stahlman et al. [169]; Kimura et al. [170]
HOX-a5 Homeobox-A5 Mesenchyme Poor airway branching; thickening of the alveolar walls Aubin et al. [163]
ALK-3 Aurora-like kinase Epithelium Impairment of lung branching; decreased cell proliferation Sun et al. [171]
Other molecular factors
Tmem 16a Transmembrane protein-16a Epithelium Abnormal tracheal cartilage development Rock et al. [172]
RARs Retinoic receptors Epithelium; mesenchyme; mesothelium Lung agenesis and hypolasia; reduction in alveolar number; tracheoesophangeal fistula Mendelsohn et al. [173]; Dickman et al. [174]; McGowan et al. [175]; Cardoso and Lü [40]
Itga-3 Integrinα-3 Epithelium Defective branching Kreidberg et al. [176]; De Arcangelis et al. [177]
Lama-5 Lamininα-5 Epithelium; mesothelium Defective lobation Schuger et al. [178]; Nguyen et al. [179]
Lmnb-1 Laminin-B1 Epithelium; mesenchyme Impaired lobation Schuger et al. [180]; Vergnes et al. [181]
PTHlh Parathyroid hormone-like peptide Epithelium Impaired branching Rubin et al. [182]