The evidence confirming the key role of Fgf10 in embryonic lung development is strong. Inflammation-induced FGF10 deficiency has been shown in preterm infants who suffer from bronchopulmonary dysplasia (BPD) but only little is known about the underlying mechanism. Thus, information regarding the role of this major signaling pathway may open new therapeutic avenues to protect or regenerate the alveolar structure in particular. To demonstrate the effect of Fgf10 deficiency for prenatal and postnatal lung development in normoxic conditions, we used a constitutive heterozygous Fgf10+/- mouse line. Lung morphometry and gene array were performed to identify changes in lung structure and global gene expression in Fgf10+/- versus Fgf10+/+ (WT) littermate lungs at E18.5. As oxygen toxicity is one of the major risk factors contributing to BPD we used the hyperoxia-induced BPD mouse model (85% oxygen from P0 P8) to investigate the impact of Fgf10 deficiency. Surprisingly, 100% of Fgf10+/- pups died within 8 days of hyperoxia injury. We therefore chose P3, a time point at which there was no observable lethality, to collect pups for further analysis involving lung morphometry, gene array, fluorescence activated cell sorting (FACS), immunofluorescence (IF), reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), and western blot. In summary, constitutive decrease in Fgf10 mRNA levels leads to lung congenital defects, which are compatible with postnatal survival, but which compromise the ability of the lungs to cope with sub-lethal hyperoxia injury. The results provide evidence that Fgf10 deficiency during embryonic lung development affects the formation of AECII quantitatively and qualitatively. Considering that the vascular compartment of the lung plays a pivotal role in the control of lung epithelial growth (Thebaud, 2007; Thebaud & Abman, 2007), we also used vascular morphometry (vessel count and vessel muscularization) to determine potential pathological changes. Furthermore, we used a previously described double transgenic system in mice to attenuate all FGFR2b ligands pre- and post-natally in the context of hyperoxia injury (Danopoulos et al., 2013; MacKenzie et al., 2015; Parsa et al., 2010; Parsa et al., 2008; Al Alam et al., 2015).
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