title: Localized Smooth Muscle Differentiation Is Essential for Epithelial Bifurcation during Branching Morphogenesis of the Mammalian Lung.
abstract: The airway epithelium develops into a tree-like structure via branching morphogenesis. Here, we show a critical role for localized differentiation of airway smooth muscle during epithelial bifurcation in the embryonic mouse lung. We found that during terminal bifurcation, changes in the geometry of nascent buds coincided with patterned smooth muscle differentiation. Evaluating spatiotemporal dynamics of α-smooth muscle actin (αSMA) in reporter mice revealed that αSMA-expressing cells appear at the basal surface of the future epithelial cleft prior to bifurcation and then increase in density as they wrap around the bifurcating bud. Disrupting this stereotyped pattern of smooth muscle differentiation prevents terminal bifurcation. Our results reveal stereotyped differentiation of airway smooth muscle adjacent to nascent epithelial buds and suggest that localized smooth muscle wrapping at the cleft site is required for terminal bifurcation during airway branching morphogenesis.
authors.affiliation: Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Mei-Fong
authors.initials: MF
authors.lastname: Pang
authors.affiliation: Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Victor D
authors.initials: VD
authors.lastname: Varner
authors.affiliation: Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Kojima
authors.affiliation: Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL 32224, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Miller
authors.affiliation: Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL 32224, USA.
authors.forename: Derek C
authors.initials: DC
authors.lastname: Radisky
authors.affiliation: Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. Electronic address: celesten@princeton.edu.
authors.forename: Celeste M
authors.initials: CM
authors.lastname: Nelson
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D004848:Epithelium / Q000196:embryology* / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000502:physiology*; D009130:Muscle, Smooth / Q000196:embryology* / Q000378:metabolism; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000199:Actins; D012333:RNA, Messenger