FGF signalling orchestrates cell-cell junctions and cell fate decisions in 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 out 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 the receptor and the specific transcriptional changes that occur in the epithelial cells upon signalling are not completely understood. Using the murine Salivary Gland (SG) as a model for 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 occur by pharmaceutical inhibition vs genetic deletion of FGF receptors and identified a dependence of FGF for the correct coordination of nerves and blood vessels growth with gland epithelium. We furthermore identified a role of FGF in establishing cell-cell junctions, crucial for epithelium architecture and integrity. Moreover, we found that FGF signalling via ERK induced bud cell fate at the expense of duct, positioning FGF at the top of the cell fate decision cascade. Altogether, our approach uncovers the many roles of FGF signalling in salivary gland branching morphogenesis.