title: Mechanically patterning the embryonic airway epithelium.
abstract: Collections of cells must be patterned spatially during embryonic development to generate the intricate architectures of mature tissues. In several cases, including the formation of the branched airways of the lung, reciprocal signaling between an epithelium and its surrounding mesenchyme helps generate these spatial patterns. Several molecular signals are thought to interact via reaction-diffusion kinetics to create distinct biochemical patterns, which act as molecular precursors to actual, physical patterns of biological structure and function. Here, however, we show that purely physical mechanisms can drive spatial patterning within embryonic epithelia. Specifically, we find that a growth-induced physical instability defines the relative locations of branches within the developing murine airway epithelium in the absence of mesenchyme. The dominant wavelength of this instability determines the branching pattern and is controlled by epithelial growth rates. These data suggest that physical mechanisms can create the biological patterns that underlie tissue morphogenesis in the embryo.
authors.affiliation: Department of Chemical & Biological Engineering, Princeton University, Princeton, NJ 08544;
authors.forename: Victor D
authors.initials: VD
authors.lastname: Varner
authors.affiliation: Department of Chemical & Biological Engineering, Princeton University, Princeton, NJ 08544;
authors.forename: Jason P
authors.initials: JP
authors.lastname: Gleghorn
authors.affiliation: Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL 32224;
authors.forename: Erin
authors.initials: E
authors.lastname: Miller
authors.affiliation: Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL 32224;
authors.forename: Derek C
authors.initials: DC
authors.lastname: Radisky
authors.affiliation: Department of Chemical & Biological Engineering, Princeton University, Princeton, NJ 08544; Department of Molecular Biology, Princeton University, Princeton, NJ 08544 celesten@princeton.edu.
authors.forename: Celeste M
authors.initials: CM
authors.lastname: Nelson
mesh_terms: D000818:Animals; D019521:Body Patterning; D049109:Cell Proliferation; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D004548:Elasticity; D004848:Epithelium / Q000196:embryology*; D005346:Fibroblast Growth Factors / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D021621:Imaging, Three-Dimensional; D007797:Laminin / Q000737:chemistry; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009024:Morphogenesis; D009924:Organ Culture Techniques / Q000379:methods; D011509:Proteoglycans / Q000737:chemistry; D012137:Respiratory System / Q000196:embryology; D015398:Signal Transduction; D013314:Stress, Mechanical; D013997:Time Factors; D014783:Viscosity
chemical_list: D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D049452:Green Fluorescent Proteins; D005346:Fibroblast Growth Factors; D003094:Collagen
keywords: buckling; instability; mechanical stress; morphodynamics; morphogenesis