Format

Send to

Choose Destination
Dev Cell. 2015 Sep 28;34(6):719-26. doi: 10.1016/j.devcel.2015.08.012. Epub 2015 Sep 18.

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

Author information

1
Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
2
Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL 32224, USA.
3
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.

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.

PMID:
26387457
PMCID:
PMC4589145
DOI:
10.1016/j.devcel.2015.08.012
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center