Alveologenesis – the repeated division and growth of alveoli to expand the surface area in the lung – is one of the least understood stages of postnatal lung development. Defective alveologenesis results in bronchopulmonary dysplasia, a disorder often observed in premature infants. FGF signalling and the extracellular matrix (ECM) protein elastin are known to be important for alveologenesis, but the underlying mechanisms are poorly understood. On p. 4563, Xin Sun and colleagues dissect the roles of FGFR3 and FGFR4 in alveologenesis. Using both global and conditional Fgfr3;4 double-mutant mouse models, they show that the earliest apparent phenotype – preceding any defects in alveolar organisation – is the improper deposition of elastin fibres. Levels of elastin protein are initially unchanged, but fibre organisation is disrupted, suggesting that this may be the underlying cause of the alveolar simplification observed in the mutants. Furthermore, the phenotype can be partially rescued by depletion of Mfap5, a regulator of elastin deposition that is upregulated in the Fgfr3;4 mutant. Lineage-specific inactivation of Fgfr3;4 demonstrated that normal alveologenesis requires functional Fgfr3 and Fgfr4 in the mesenchyme but not the epithelium, which is consistent with the known role of fibroblasts in ECM organisation. The authors suggest that a defective elastin ECM physically interferes with alveolar septa formation, resulting in simplified alveoli characteristic of bronchopulmonary dysplasia.
- © 2017. Published by The Company of Biologists Ltd
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