Actively migrating cells generate protrusive
forces through lamellipodia or filopodia, which
are driven by actin polymerization ( 26 ). Gut epi-
thelial cells are columnar, apicobasally polarized,
and not known to have lamellipodia. To assess
if gut epithelial cells have cryptic protrusions,
we generated a mouse that mosaically expresses
LifeAct-mCherry in the gut epithelium, to follow
F-actin in individual cells (Fig. 3A). We found
that enterocytes have small, F-actin–rich basalfeet in contact with the basement membrane,
pointing in the direction of cell movement (Fig.
3, B to D). Membrane-targeted GFP also high-
lighted basal protrusions in Villin:CreERT2/mTmG
reporter mice (fig. S6A). Radial distance mapKrndijaet al.,Science 365 , 705–710 (2019) 16 August 2019 3of6
Fig. 2. Epithelial cells
migrate collectively with
increasing velocity and
create a gradient of tissue
tension along the villi.
(A) Predicted cell velocity
profiles along the crypt-villus
axis depending on the level
of active migratory force.
(B) EdU pulse-chase assay
(top); box-and-whisker plot
(bottom left) and EdU fronts’
position (scheme; bottom
middle); EdU fronts plotted as
a function of time (bottom
right). (C) Montage from a
time-lapse movie of gut
explants (Villin:CreERT2/
mTmG; maximum projection
of 50mm); dashed line, villus.
(Inset) A magnified region.
Scale bar, 50mm. (D) Top:
Cell segmentation (cyan) and
cell tracks (white) from the
experiment shown in (C).
Dashed line, villus. Scale bar,
50 mm. Bottom: Mean cell
speeds plotted against relative
cell position. (E) Average cell
velocity plotted against villus
axis, overlaid with model pre-
dictions. (F) Top: Skeletonized
and tracked images from a
time-lapse movie. Newly
formed junctions (magenta),
junctions formed after
rearrangements (black),
delamination (green), or
division (none). Inset shows a
magnified region. Scale bars,
20 mm. Bottom: Analysis of
tissue deformation. Circles
represent size change; bars
represent pure shear
(contraction-elongation).
(G) Montage showing images
before and after laser ablation
in lower villus (left-hand panel)
and upper villus (right-hand
panel). Scale bars, 20mm.
Magnified regions: Postabla-
tion images (post-cut, red)
overlaid with preablation
images (pre-cut, green). Scale
bars, 5mm. (H) Left: Radar
chart showing mean relaxation
speed per four directions in
lower (blue) and upper (purple) villus regions [as schematized in (G)]. Middle: Vertex separatione(t) plot in function of time, for lower (purple) and upper
(blue) villus region. Right: Initial recoil speed for lower and upper villus region. *P< 0.05.
RESEARCH | REPORT