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Cell. 2015 Oct 8;163(2):394-405. doi: 10.1016/j.cell.2015.09.021. Epub 2015 Oct 1.

Formation of a Neurosensory Organ by Epithelial Cell Slithering.

Author information

1
Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305-5307, USA; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305-5307, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305-5307, USA.
2
Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305-5307, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305-5307, USA. Electronic address: krasnow@stanford.edu.

Abstract

Epithelial cells are normally stably anchored, maintaining their relative positions and association with the basement membrane. Developmental rearrangements occur through cell intercalation, and cells can delaminate during epithelial-mesenchymal transitions and metastasis. We mapped the formation of lung neuroepithelial bodies (NEBs), innervated clusters of neuroendocrine/neurosensory cells within the bronchial epithelium, revealing a targeted mode of cell migration that we named "slithering," in which cells transiently lose epithelial character but remain associated with the membrane while traversing neighboring epithelial cells to reach cluster sites. Immunostaining, lineage tracing, clonal analysis, and live imaging showed that NEB progenitors, initially distributed randomly, downregulate adhesion and polarity proteins, crawling over and between neighboring cells to converge at diametrically opposed positions at bronchial branchpoints, where they reestablish epithelial structure and express neuroendocrine genes. There is little accompanying progenitor proliferation or apoptosis. Activation of the slithering program may explain why lung cancers arising from neuroendocrine cells are highly metastatic.

PMID:
26435104
PMCID:
PMC4597318
DOI:
10.1016/j.cell.2015.09.021
[Indexed for MEDLINE]
Free PMC Article

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