Journal
DEVELOPMENTAL CELL
Volume 34, Issue 6, Pages 719-726Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2015.08.012
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Funding
- NIH [GM083997, HL110335, HL118532, HL120142]
- NSF [CMMI-1435853]
- David and Lucile Packard Foundation
- Alfred P. Sloan Foundation
- Camille and Henry Dreyfus Foundation
- Susan G. Komen for the Cure
- Burroughs Wellcome Fund
- Swedish Society for Medical Research (SSMF)
- Lidow Senior Thesis Fund
- Div Of Civil, Mechanical, & Manufact Inn
- Directorate For Engineering [1435853] Funding Source: National Science Foundation
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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 alpha-smooth muscle actin (alpha SMA) in reporter mice revealed that alpha SMA-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.
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