Title | Localized Smooth Muscle Differentiation Is Essential for Epithelial Bifurcation during Branching Morphogenesis of the Mammalian Lung. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Kim, HYoung, Pang, M-F, Varner, VD, Kojima, L, Miller, E, Radisky, DC, Nelson, CM |
Journal | Dev Cell |
Volume | 34 |
Issue | 6 |
Pagination | 719-26 |
Date Published | 2015 Sep 28 |
ISSN | 1878-1551 |
Keywords | Actins, 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> |
DOI | 10.1016/j.devcel.2015.08.012 |
Alternate Journal | Dev Cell |
PubMed ID | 26387457 |
PubMed Central ID | PMC4589145 |
Grant List | R21 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 |