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of an inner endodermal epithelium and an outer mesenchyme. The expression
pattern of specific FGFs at distinct steps of bud emergence controls regional
endodermal cell proliferation.
Isotype FGF10 is produced by the mesenchyme at the earliest stages of lung-
bud formation with 2 primordial buds from the trachea, from which the bronchial
tree arises using a process of elongation, budding, and branching. Agent FGF10
stimulates proliferation of endodermal cells in the apical region of developing
buds [
1395
].
Epidermal Growth Factor
Epidermal growth factor, transforming growth factor-
, and amphiregulin are
produced by the mesenchyme and act via the common EGFR receptor [
1396
].
α
Hepatocyte Growth Factor
Hepatocyte growth factor is produced by the mesenchyme and its receptor is
confined to the epithelium [
1396
]. Agent HGF supports action of other growth
factors in branching genesis.
Insulin-like Growth Factor
Concentrations of insulin-like growth factors IGF1 and IGF2 as well as that of their
receptors do not change during gestation; IGF-binding proteins (IGFBP1-IGFBP6)
are developmentally regulated [
1396
]. Receptor of IGF1 is necessary to avoid lung
hypoplasia, but does not intervene in branching formation. Receptor of IGF2 is
required for normal alveolus development.
Platelet-Derived Growth Factor
Production of platelet-derived growth factor is restricted to the epithelium, whereas
its cognate receptors localize to the mesenchyme [
1396
]. Homodimer PDGFaa
contributes to branching regulation. Protomer PDGFa is required for alveolus
septation.
Transforming Growth Factor
Transforming growth factor-
β
1 to -3 as well as receptors T
β
R1 and T
β
R2 are
involved in embryonic lungs. Agents TGF
2 are produced by the
mesenchyme and epithelium, respectively [
1396
]. They impede the generation
of pulmonary branching via T
β
1andTGF
β
β
R2. On the other hand, TGF
β
3 stimulates lung
development.
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