Lung development is controlled by regulatory networks governing 
mesenchymal-epithelial interactions. Transcription factors and signaling 
molecules are known to participate in this process, yet little is known about 
the post-transcriptional regulation of these networks. Here we demonstrate that 
the RNA-binding protein (RBP) HuR is an essential regulator of mesenchymal 
responses during lung branching. Its epiblast-induced deletion blocked the 
morphogenesis of distal bronchial branches at the initiation of the 
pseudoglandular stage. The phenotype originated from defective mesenchymal 
responses since the conditional restriction of HuR deletion in epithelial 
progenitors did not affect distal branching or the completion of lung 
maturation. The loss of HuR resulted in the reduction of the key inducer of bud 
outgrowth and endodermal branching, FGF10 and one of its putative 
transcriptional regulators, Tbx4. Furthermore, exogenous FGF10 could rescue the 
branching defect of affected lung buds. HuR was found to bind and control the 
Fgf10 and Tbx4 mRNAs; as a result its deletion abolished their inducible 
post-transcriptional regulation by the mesenchymal regulator FGF9. Our data 
reveals HuR as the first RBP identified to play a dominant role in lung 
development and as a key post-transcriptional regulator of networks guiding 
tissue remodeling during branching morphogenesis.