Title: Mesenchymal fluidity, matrix transport, and tissue morphogenesis

Author (Invited): Celeste Nelson, Princeton University

Abstract:

Reciprocal signaling between an epithelium and its surrounding mesenchyme is common during morphogenesis. These epithelial-mesenchymal interactions are particularly evident in tissues that undergo branching morphogenesis, such as the airway epithelium of the lung. Here, we found that reciprocal interactions between the epithelium and mesenchyme induce fluidity within the mesenchymal tissue compartment that drives remodeling of the extracellular matrix (ECM) during morphogenesis of the embryonic chicken lung. RNA-Seq analysis revealed changes in the expression of genes associated with integrin signaling and ECM remodeling. Consistently, we found that as branches extend, the mesenchymal ECM protein tenascin-C (TNC) accumulates in the mesenchyme several cell diameters away from the branch tip. Despite its pattern of accumulation, TNC is expressed exclusively by airway epithelial cells, which activate focal adhesion kinase (FAK) to induce TNC expression. We found that branch extension coincides with the deformation of adjacent mesenchymal cells into elongated geometries, which correlates with an increase in the fluidity of the mesenchyme at branch tips. This local increase in mesenchymal movement transports TNC from the epithelial surface into the mesenchyme. These data reveal novel epithelial-mesenchymal interactions that direct ECM remodeling during airway branching morphogenesis.