Localized Smooth Muscle Differentiation Is Essential for Epithelial Bifurcation during Branching Morphogenesis of the Mammalian Lung.

TitleLocalized Smooth Muscle Differentiation Is Essential for Epithelial Bifurcation during Branching Morphogenesis of the Mammalian Lung.
Publication TypeJournal Article
Year of Publication2015
AuthorsKim, HYoung, Pang, M-F, Varner, VD, Kojima, L, Miller, E, Radisky, DC, Nelson, CM
JournalDev Cell
Volume34
Issue6
Pagination719-26
Date Published2015 Sep 28
ISSN1878-1551
KeywordsActins, Animals, Blotting, Western, Cell Differentiation, Cells, Cultured, Epithelium, Female, Fluorescent Antibody Technique, Lung, Mice, Mice, Transgenic, Morphogenesis, Muscle, Smooth, Organ Culture Techniques, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger
Abstract

<p>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.</p>

DOI10.1016/j.devcel.2015.08.012
Alternate JournalDev. Cell
PubMed ID26387457
PubMed Central IDPMC4589145
Grant ListR21 HL110335 / HL / NHLBI NIH HHS / United States
HL110335 / HL / NHLBI NIH HHS / United States
R21 HL118532 / HL / NHLBI NIH HHS / United States
R01 GM083997 / GM / NIGMS NIH HHS / United States
R01 HL120142 / HL / NHLBI NIH HHS / United States
HL118532 / HL / NHLBI NIH HHS / United States
GM083997 / GM / NIGMS NIH HHS / United States
HL120142 / HL / NHLBI NIH HHS / United States