Advective Transport of Tenascin-C During Lung Branching Morphogenesis from the Airway Epithelium into the Mesenchyme

Abstract

Reciprocal signaling between the epithelium and surrounding mesenchyme directs the process of branching morphogenesis during the development of the fetal lung. Recent work in our group has revealed that the developmental glycoprotein, tenascin-C (TNC), accumulates in the mesenchyme surrounding growing airways in the developing avian lung. Using in situ hybridization and immunofluorescence analysis, we determined that the synthesis of TNC is restricted to the airway epithelium in the embryonic avian lung despite its accumulation in the mesenchyme. This finding challenges the current dogma about this protein and raise the question of how a large molecule like TNC can be transported across significant distances. Passive transport was observed within the extracellular matrix surrounding the airway epithelium using cultured lungs with fluorescent beading tracking. In silico simulations were performed using the finite element method to examine the effects of the rates of branch elongation and diffusion coefficients. These simulations suggested that diffusion alone is insufficient to account for the transport of TNC and that an additional convective force is necessary. Elucidating the mechanisms necessary for the transport of large molecules may prove useful for engineering complex branched tissues for the treatment of damaged organs.