Directed Migration of Pulmonary Neuroendocrine Cells toward Airway Branches Organizes the Stereotypic Location of Neuroepithelial Bodies

Cell Rep. 2015 Dec 29;13(12):2679-86. doi: 10.1016/j.celrep.2015.11.058. Epub 2015 Dec 17.


The airway epithelium consists of diverse cell types, including neuroendocrine (NE) cells. These cells are thought to function as chemoreceptors and as a component of the stem cell niche as well as the cells of origin in small-cell lung cancer. NE cells often localize at bifurcation points of airway tubes, forming small clusters called neuroepithelial bodies (NEBs). To investigate NEB development, we established methods for 3D mapping and ex vivo 4D imaging of developing lungs. We found that NEBs localize at stereotypic positions in the bifurcation area irrespective of variations in size. Notch-Hes1 signaling contributes to the differentiation of solitary NE cells, regulating their number but not localization. Live imaging revealed that individual NE cells migrate distally to and cluster at bifurcation points, driving NEB formation. We propose that NEB development is a multistep process involving differentiation of individual NE cells and their directional migration to organize NEBs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / physiology*
  • Immunohistochemistry
  • Lung / cytology*
  • Lung / metabolism
  • Mice
  • Neuroendocrine Cells / cytology*
  • Neuroendocrine Cells / metabolism*
  • Neuroepithelial Bodies / cytology*
  • Neuroepithelial Bodies / metabolism