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Active cell migration is critical for steady-state epithelial turnover in the gut

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Science  16 Aug 2019:
Vol. 365, Issue 6454, pp. 705-710
DOI: 10.1126/science.aau3429

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Active migration renews gut epithelia

Epithelial tissues are continuously renewed throughout adult life, and the gut epithelium is the fastest self-renewing tissue in mammals. Over 3 days or so, epithelial cells migrate from the crypts, where they are born, to the tips of the villi, where they die. It is commonly believed that migration is strictly passive, driven by mitotic pressure in crypts—as cells divide, they push their neighbors upward. Krndija et al. now challenge this concept and show that cells migrate actively, using actin-rich basal protrusions oriented in the direction of migration (see the Perspective by Jansen).

Science, this issue p. 705; see also p. 642

Abstract

Steady-state turnover is a hallmark of epithelial tissues throughout adult life. Intestinal epithelial turnover is marked by continuous cell migration, which is assumed to be driven by mitotic pressure from the crypts. However, the balance of forces in renewal remains ill-defined. Combining biophysical modeling and quantitative three-dimensional tissue imaging with genetic and physical manipulations, we revealed the existence of an actin-related protein 2/3 complex–dependent active migratory force, which explains quantitatively the profiles of cell speed, density, and tissue tension along the villi. Cells migrate collectively with minimal rearrangements while displaying dual—apicobasal and front-back—polarity characterized by actin-rich basal protrusions oriented in the direction of migration. We propose that active migration is a critical component of gut epithelial turnover.

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