FGF receptors control alveolar elastogenesis.
Development
; 144(24): 4563-4572, 2017 12 15.
Article
en En
| MEDLINE
| ID: mdl-29122839
ABSTRACT
Alveologenesis, the final step of lung development, is characterized by the formation of millions of alveolar septa that constitute the vast gas-exchange surface area. The genetic network driving alveologenesis is poorly understood compared with earlier steps in lung development. FGF signaling through receptors Fgfr3 and Fgfr4 is crucial for alveologenesis, but the mechanisms through which they mediate this process remain unclear. Here we show that in Fgfr3;Fgfr4 (Fgfr3;4) global mutant mice, alveolar simplification is first observed at the onset of alveologenesis at postnatal day 3. This is preceded by disorganization of elastin, indicating defects in the extracellular matrix (ECM). Although Fgfr3 and Fgfr4 are expressed in the mesenchyme and epithelium, inactivation in the mesenchyme, but not the epithelium, recapitulated the defects. Expression analysis of components of the elastogenesis machinery revealed that Mfap5 (also known as Magp2), which encodes an elastin-microfibril bridging factor, is upregulated in Fgfr3;4 mutants. Mfap5 mutation in the Fgfr3;4 mutant background partially attenuated the alveologenesis defects. These data demonstrate that, during normal lung maturation, FGF signaling restricts expression of the elastogenic machinery in the lung mesenchyme to control orderly formation of the elastin ECM, thereby driving alveolar septa formation to increase the gas-exchange surface.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Alveolos Pulmonares
/
Proteínas de la Matriz Extracelular
/
Proteínas Contráctiles
/
Organogénesis
/
Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos
/
Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos
Límite:
Animals
Idioma:
En
Revista:
Development
Asunto de la revista:
BIOLOGIA
/
EMBRIOLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos