First published online June 14, 2004
doi: 10.1242/10.1242/dev.01253
Development 131, 3021-3034 (2004)
Published by The Company of Biologists 2004
Parallels between tissue repair and embryo morphogenesis
Paul Martin and
Susan M. Parkhurst
Departments of Physiology and Biochemistry, University of Bristol, School
of Medical Sciences, University Walk, Bristol BS8 1TD, UK Division of Basic
Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North,
A1-162, PO Box 19024, Seattle, WA 98109-1024, USA
View larger version (87K):
[in a new window]
|
Fig. 1. The cellular players in the healing of a skin wound. The wound is first
‘plugged’ with a fibrin clot, which is infiltrated by inflammatory
cells, fibroblasts and a dense plexus of capillary vessels. The epidermis
migrates forwards from the edges of the wound and from the cut remnants of
hair follicles. Neutrophils and macrophages (blue) emigrate from the wound
capillaries into the wound granulation tissue where they kill microbes, engulf
cell and matrix debris, and release signals that act on the host wound
tissues. Image modified, with permission, from Martin
(Martin, 1997 ).
|
|
View larger version (137K):
[in a new window]
|
Fig. 3. Epidermal hole closure as part of natural morphogenetic episodes.
Drosophila dorsal closure and C. elegans ventral enclosure.
(A-D) Confocal micrographs of the dorsal surface of successively older
Drosophila embryos expressing  -catenin-GFP that depict the
four phases of dorsal closure: (A) initiation; (B) epithelial sweeping; (C)
zippering; and (D) termination. LE, leading edge epidermis; AS, amnioserosa;
VE, ventral ectoderm. (E-H) Scanning electron micrographs of the ventral
surface of successively older C. elegans embryos similarly depicting
dorsal intercalation and the three phases of ventral enclosure: (E) dorsal
intercalation; (F) leading cell migration; (G) leading cell junction formation
and fusion; and (H) ventral pocket enclosure. Leading edge cells (LE) are
marked with an asterisk. LSH, lateral seam hypodermis; VH, ventral hypodermis.
Anterior is towards the left in all images. (A-D) Courtesy of Sarah Woolner;
(E-H) courtesy of Jim Priess.
|
|
View larger version (69K):
[in a new window]
|
Fig. 4. Lamellipodial crawling versus purse-string closure of an in vitro
epithelial wound. (A) A temporal series that illustrates how the contractile
actin purse-string acts to draw a wound epidermis closed. The individual actin
filaments (green bars) anchor to adherens junctions (blue rectangles) formed
between adjacent cells. Contraction of the actin cable in each cell leads to
apical cell constriction and reduced wound circumference. As wound closure
proceeds, some cells are squeezed out of the front row such that fewer
epithelial cells remain in the front row. The remaining cells form new
adherens junctions and apical actin cable contraction continues until the
contralateral cells meet and fuse. Asterisks indicate cells that will be lost
from the leading edge; nuclei are red. (B) Repair of wounds made in monolayers
of the gut epithelial cell line Caco2BBE is achieved by
lamellipodial crawling or actin purse-string contraction, or a combination of
both. In this wound, one group of leading-edge cells is being drawn forwards
by contraction of an actin cable (arrows), as occurs during embryonic repair;
while other cells are clearly extending lamellae (arrowheads) and crawling
forwards, as occurs during repair of an adult skin wound [image courtesy of
Jane Brock; reproduced, with permission, from Jacinto et al.
(Jacinto et al., 2000)]. Green
staining is fluorescein isothiocyanate/phalloidin-tagged filamentous actin;
red staining is the nuclear dye 7AAD.
|
|
View larger version (103K):
[in a new window]
|
Fig. 5. Parallels between Drosophila dorsal closure and wound healing. (A)
Confocal micrograph of a dorsal closure stage Drosophila embryo
expressing GFPactin to reveal the actin cable and filopodial protrusions that
drive dorsal closure. (B) A transmission electron micrograph section cut
through the zippering zone shows how the filopodia of opposing epithelial
cells (arrows) interdigitate and prime the formation of adhesions between the
two epithelial fronts. (C,D) Equivalent images from laser wounds in similarly
staged embryos that show how opposing epithelial fronts (arrows in D) are
knitted together using the same actin-based machineries as for dorsal closure.
(E) A temporal series that illustrates how filopodial interdigitation is
believed to prime the assembly of mature adherens junctions. Adjacent cells
extend filopodia towards each other, which interdigitate, with actin (red),
catenins and cadherins (yellow) localizing to the filopodial tips and points
of contact. The filopodia then shorten, drawing the cells together. This
filopodial zippering is propagated to the edge of the cell resolving into
mature junctions. (A-D) Courtesy of Will Wood; (E) courtesy of Craig
Magie.
|
|
View larger version (157K):
[in a new window]
|
Fig. 6. Eyelid fusion in the mouse. (A) A scanning electron micrograph of the mouse
eye at E15, when eyelids are just beginning to advance forwards over the
corneal epithelium. (B) A transverse section through the eye taken at the
level indicated by the broken line in A. (C) Transmission electron microscopy
of the leading edge cells (corresponding to box in B) shows expression of
numerous filopodia. (D) When the two eyelids confront one another at the
anterior and posterior canthi, the filopodia of opposing epithelial cells
interdigitate, just as during Drosophila dorsal closure.
|
|
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
© The Company of Biologists Ltd 2004
30-minute intervals from a movie
of a laser wound (broken lines) made to the ventral epithelial surface of a
Drosophila embryo expressing