FGF signalling orchestrates multiple roles during salivary gland branching morphogenesis

The function of the organs in our body is intrinsically related to their form, acquired during embryonic development. Many epithelial organs such as lung, kidney, pancreas or salivary glands branch during morphogenesis to optimise the available surface of the epithelium. In the embryo, Fibroblast Growth Factor (FGF) ligands secreted by the surrounding mesenchyme control both elongation and branching of the epithelium. However, the intracellular pathways activated downstream of the receptor and the specific transcriptional changes that occur in the epithelial cells upon signalling are not completely understood. Using the murine salivary gland as a model of branching morphogenesis, we have taken advantage of its ease of ex vivo culture to identify the molecular players downstream of FGF during branching. We compared the morphological and transcriptional changes that occurred after pharmaceutical inhibition vs genetic deletion of FGF receptors and identified a dependence of FGF for the correct coordination of nerve and blood vessel growth with the budding gland epithelium. Furthermore, we identified a role for FGF in establishing cell-cell junctions, crucial for epithelium architecture and integrity. Importantly, FGF signalling via ERK was shown to be key for upregulation of the mature bud cell marker cKIT, suggesting FGF could influence cell fate decisions during gland development. Altogether, our approach uncovers the many roles of FGF signalling in salivary gland branching morphogenesis.