Biology Reference
In-Depth Information
just the parts that are free to make further progress, and the cells will move side-by-side to
their common goal.
5
In dense situations, this effect causes cells to make rafts and finally
a whole collective in which side-to-side shoving is kept at a minimum and leading edges
are confined to the front of the group, or to any internal gaps that might open when leading
cells pull away from their followers. In this way, contact inhibition converts a dense set of
motile cells that would otherwise generate a serious traffic jam into a highly correlated group
that can advance as one.
Another way in which dense groups of cells can coordinate their motion is plithotaxis, the
guidance of cells through alignment with mechanical forces generated by the whole group.
6,7
Cells show a preference for migration along the direction at which normal stress (tension/
compression) is highest and shear stress (force parallel to the membrane) lowest. In real cells
in culture, there is local correlation in the direction of stress and therefore in the direction of
active movement. Like other mechanical mechanisms, plithotaxis is powerful because of its
scalability; detecting mechanical stress can be done the same way in a small or very large
group of cells, and thus escapes from the limitations of scale that affect mechanisms such
as sensing chemical gradients. This theme will be taken up again in Chapter 23, in the context
of growth control.
CASE STUDY: COLLECTIVE CELL MIGRATION
BY THE NEURAL CREST
Cells of the neural crest stream away from the dorsal surface of the neural tube at very
high density and so on to form many different parts of the vertebrate body, including the
peripheral nervous system, skin pigment cells, a significant part of the adrenal gland and
a large proportion of the face.
8
For at least the first parts of their journey, crest cells seem
to migrate as a collective even if this later breaks up.
9
The migration of the cephalic neural crest of X. laevis is guided by both haptotaxis and by
chemotaxis, in this case up a gradient of the ligand Sdf1 that is detected by the cells' receptor,
Cxcr4.
Ref
10
Normally, the cells migrate as a large group, cells being attracted to one another
because each releases the complement peptide C3a and each bears the C3a receptor which
organizes positive chemotaxis.
11
Within the migrating group, only leading cells show signif-
icant leading edge activity. The cells behind them move along anyway, either with the aid of
cryptic motility or possibly by being dragged: the continual progress of dividing (and there-
fore temporarily non-motile) cells in the group and the progress of cells expressing dominant
negative Cxcr4 in an otherwise wild-type group does argue for the idea of dragging along,
although a consideration of the magnitude of the forces needed implies that not all inner cells
can be idle.
12
Presumably, as the leading edge cells draw ahead, the cells behind shuffle up,
with limited motile activity (there being no need to explore) driven by C3a. The lack of exten-
sive motile activity in the bulk of the group is accounted for by contact inhibition of locomo-
tion mediated by the homophilic cell adhesion molecule, N-cadherin. N-cadherin
d
which
like most cell-cell adhesion molecules
d
has a signalling function as well, signals via Rho
to organize actin as stress fibres in preference to a leading edge.
13
The chemotactic response of the neural crest cells for Sdf1 is dependent on N-cadherin
mediated contact. Chemotaxis disappears if cells are disaggregated before the assay,
