Title | Mesenchymal proteases and tissue fluidity remodel the extracellular matrix during airway epithelial branching in the embryonic avian lung. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Spurlin, JW, Siedlik, MJ, Nerger, BA, Pang, M-F, Jayaraman, S, Zhang, R, Nelson, CM |
Journal | Development |
Volume | 146 |
Issue | 16 |
Date Published | 2019 Aug 19 |
ISSN | 1477-9129 |
Keywords | Animals, Basement Membrane, Body Fluids, Cell Shape, Chick Embryo, Extracellular Matrix, Lung, Matrix Metalloproteinases, Mesoderm, Morphogenesis, Respiratory Mucosa, Tenascin, Tissue Culture Techniques |
Abstract | <p>Reciprocal epithelial-mesenchymal signaling is essential for morphogenesis, including branching of the lung. In the mouse, mesenchymal cells differentiate into airway smooth muscle that wraps around epithelial branches, but this contractile tissue is absent from the early avian lung. Here, we have found that branching morphogenesis in the embryonic chicken lung requires extracellular matrix (ECM) remodeling driven by reciprocal interactions between the epithelium and mesenchyme. Before branching, the basement membrane wraps the airway epithelium as a spatially uniform sheath. After branch initiation, however, the basement membrane thins at branch tips; this remodeling requires mesenchymal expression of matrix metalloproteinase 2, which is necessary for branch extension but for not branch initiation. As branches extend, tenascin C (TNC) accumulates in the mesenchyme several cell diameters away from the epithelium. Despite its pattern of accumulation, TNC is expressed exclusively by epithelial cells. Branch extension coincides with deformation of adjacent mesenchymal cells, which correlates with an increase in mesenchymal fluidity at branch tips that may transport TNC away from the epithelium. These data reveal novel epithelial-mesenchymal interactions that direct ECM remodeling during airway branching morphogenesis.</p> |
DOI | 10.1242/dev.175257 |
Alternate Journal | Development |
PubMed ID | 31371376 |
PubMed Central ID | PMC6737900 |
Grant List | R21 HL110335 / HL / NHLBI NIH HHS / United States F32 HL137273 / HL / NHLBI NIH HHS / United States R01 CA187692 / CA / NCI NIH HHS / United States R21 HL118532 / HL / NHLBI NIH HHS / United States / HHMI / Howard Hughes Medical Institute / United States R01 HL120142 / HL / NHLBI NIH HHS / United States R01 HD099030 / HD / NICHD NIH HHS / United States |