@article{e548167e74824904b13822ffaf945fbc,
title = "Mesenchymal proteases and tissue fluidity remodel the extracellular matrix during airway epithelial branching in the embryonic avian lung",
abstract = "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.",
keywords = "Jamming, Mechanical stress, Tissue morphodynamics",
author = "Spurlin, {James W.} and Siedlik, {Michael J.} and Nerger, {Bryan A.} and Pang, {Mei Fong} and Sahana Jayaraman and Rawlison Zhang and Nelson, {Celeste M.}",
note = "Funding Information: This work was supported in part by grants from the National Institutes of Health (HL118532, HL120142 and CA187692), the National Science Foundation (CMMI-1435853), the David and Lucile Packard Foundation, the Camille and Henry Dreyfus Foundation, and the Burroughs Wellcome Fund. J.W.S. was supported in part by an National Research Service Award Postdoctoral Fellowship (HL137273). M.J.S. was supported in part by the National Science Foundation Graduate Research Fellowship Program and the Wallace Memorial Fellowship in Engineering. B.A.N. was supported in part by a postgraduate scholarship-doctoral (PGS-D) from the Natural Sciences and Engineering Research Council of Canada. M.F.P. was supported in part by postdoctoral fellowships from the Svenska S{\"a}llskapet f{\"o}r Medicinsk Forskning (SSMF) and the New Jersey Commission on Cancer Research (NJCCR). C.M.N. was supported in part by a Faculty Scholars Award from the Howard Hughes Medical Institute. Deposited in PMC for release after 12 months. Funding Information: The authors would like to thank the members of the Tissue Morphodynamics Group for helpful discussions. This work was supported in part by grants from the National Institutes of Health (HL118532, HL120142 and CA187692), the National Science Foundation (CMMI-1435853), the David and Lucile Packard Foundation, the Camille and Henry Dreyfus Foundation, and the Burroughs Wellcome Fund. J.W.S. was supported in part by an National Research Service Award Postdoctoral Fellowship (HL137273). M.J.S. was supported in part by the National Science Foundation Graduate Research Fellowship Program and the Wallace Memorial Fellowship in Engineering. B.A.N. was supported in part by a postgraduate scholarship-doctoral (PGS-D) from the Natural Sciences and Engineering Research Council of Canada. M.F.P. was supported in part by postdoctoral fellowships from the Svenska S?llskapet f?r Medicinsk Forskning (SSMF) and the New Jersey Commission on Cancer Research (NJCCR). C.M.N. was supported in part by a Faculty Scholars Award from the Howard Hughes Medical Institute. Deposited in PMC for release after 12 months. Publisher Copyright: {\textcopyright} 2019. Published by The Company of Biologists Ltd",
year = "2019",
doi = "10.1242/dev.175257",
language = "English (US)",
volume = "146",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "16",
}