Lateral adhesion drives reintegration of misplaced cells into epithelial monolayers
Nature Cell Biology
MetadataShow full item record
Bergstralh, D., Lovegrove, H. E., & St Johnston, D. (2015). Lateral adhesion drives reintegration of misplaced cells into epithelial monolayers. Nature Cell Biology, 17 1497-1503. https://doi.org/10.1038/ncb3248
Cells in simple epithelia orient their mitotic spindles in the plane of the epithelium so that both daughter cells are born within the epithelial sheet. This is assumed to be important to maintain epithelial integrity and prevent hyperplasia, because misaligned divisions give rise to cells outside the epithelium. Here we test this assumption in three types of Drosophila epithelium; the cuboidal follicle epithelium, the columnar early embryonic ectoderm, and the pseudostratified neuroepithelium. Ectopic expression of Inscuteable in these tissues reorients mitotic spindles, resulting in one daughter cell being born outside the epithelial layer. Live imaging reveals that these misplaced cells reintegrate into the tissue. Reducing the levels of the lateral homophilic adhesion molecules Neuroglian or Fasciclin 2 disrupts reintegration, giving rise to extra-epithelial cells, whereas disruption of adherens junctions has no effect. Thus, the reinsertion of misplaced cells seems to be driven by lateral adhesion, which pulls cells born outside the epithelial layer back into it. Our findings reveal a robust mechanism that protects epithelia against the consequences of misoriented divisions.
The authors are grateful to R. Nieuwburg, the St Johnston group, and other Gurdon Institute members for suggestions. We thank the Bloomington Stock Center, J. Knoblich, and the TRiP at Harvard Medical School (NIH/NIGMS R01-GM084947) for fly stocks. We thank N. Lowe for technical assistance. This work was supported by a Wellcome Trust Principal Fellowship to D.St.J. (080007), and by core support from the Wellcome Trust (092096) and Cancer Research UK (A14492). D.T.B. was supported by a Marie Curie Fellowship and the Wellcome Trust. H.E.L. was supported by a Herchel Smith Studentship.
Cancer Research UK (A14492)
Wellcome Trust (095927/B/11/Z)
Wellcome Trust (092096/Z/10/Z)
Wellcome Trust (080007/Z/06/Z)
External DOI: https://doi.org/10.1038/ncb3248
This record's URL: https://www.repository.cam.ac.uk/handle/1810/251246