Biology Reference
In-Depth Information
WOUND HEALING IN THE EMBRYO
Wounds in the skin or cornea of mammalian and avian embryos heal by a process similar
to dorsal closure in D. melanogaster. While wound healing might be seen to be of only periph-
eral relevance to a topic centred on mechanisms of normal morphogenesis, it provides a very
useful model precisely because wounds do not take place at stereotyped, predictable times
and places. The construction and activation of the healing mechanism therefore has to be
by local, adaptive self-organization.
When a small wound is made in embryonic skin, the undamaged tissue moves across the
hole and seals it up perfectly and scarlessly. Shortly after wound formation, cells near the edge
show a planar polarization that is revealed by their centrosome-nucleus axis, which swings
around to orientate the centrosome towards the wound edge and the nucleus away from
it.
14
A band of actin-myosin cables, connected between cells using adherens junctions, forms
just under the edges of the 'free' lateral membranes that border the wound.
15
The cable is
similar to that seen in D. melanogaster's dorsal closure, and it seems to perform a similar func-
tion: if actin polymerization is blocked using cytochalasinD, cables fail to formand the wound
fails to close.
16
As in dorsal closure, the actin cable is associated with myosin and is formed
under the action of Rho GTPase
17
and JNK is important in locating the actin-myosin cable.
5
Mammalian homologues of the proteins involved in the planar polarity system described in
Chapter 16 are also important in orientating cable assembly,
18
although it is not clear whether
these proteins are needed to give the cells a sense of direction (which could instead be
imparted biophysically, as described in the next paragraph) or just to activate effector path-
ways. To repeat a warning in Chapter 16, the presence of a protein known to be involved in
planar cell polarity in some other system is not rigorous proof that it has anything to do
with planar polarity in this one. The meeting of cells and their 'zipping up' uses exploratory
filopodia whose action is very similar to that seen in dorsal closure.
19
The 'unplanned' nature of embryonic wounds makes the self-organizing properties of the
actin cable system easier to study than in situations where 'pre-programming' of cells may be
involved. There are at least two necessary aspects to the self-organization of the wound-
closing actin cable: its expression in the correct parts of cells that appose the wound edge,
and its disappearance from cells that have already zipped up. The regulation of assembly
and disassembly has not been studied in complete detail in the wound system, but findings
from that system can be combined with studies in simple cell culture to suggest a simple and
automatic mechanism for cable regulation.
Cells in the unwounded epithelium are in tension; that is obvious from the way that
a wound made by a fine needle or blade gapes open. Because of the positive relationship
between the stability of actin/myosin fibres and the tension they carry (Chapter 5), contrac-
tile actin bundles concentrate along lines of tension that, in an unwounded epithelium, tend
to be spread evenly around the adhesive junctions of the cell. If the epithelium is wounded,
tension becomes greater at the edge of the wound and greatest where the radius of curvature
of the tissue is smallest.
)
Epithelial cells subjected to increased tension in culture respond by
)
At the end of a cut in a tissue being stressed at right angles to the cut, application of Inglis' Law states that
stress on the tissue at the tip of the cut is approximately s.(1
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2
O
(L/r)), where s is the stress in the uncut
tissue, L half length of the cut and r the radius of its end.
