Guidance by Contact - Mechanisms of Morphogenesis - page 130

produce fibres that lie along the direction of normal cell migration. These fibres are the result
of activity in the cells that secrete the fibronectin and seem to rely on mechanical force exerted
by the actin/myosin cytoskeleton acting via integrins. Interference either with fibronectin-
binding integrins using the competitor peptide sequence, GRGDSP, or interference with
the actin cytoskeleton using cytochalasin B, blocks the formation of fibronectin fibres. The
matrix laid down by a blastocoel roof that is cultured in the presence of either of these drugs
is rich in fibronectin but has no aligned fibres. Significantly, mesodermal cells plated on to it
still adhere normally and still move, but their movement is now undirected and random. 49
Clearly, the alignment of fibres is an important directional cue for mesodermal cells. The
mechanism by which cells can be guided by aligned fibres has not been investigated in detail.
Simple arguments based on adhesion, being more stable on fibres than between them, may
explain a preference for following fibres but cannot in itself explain a preference for going one
way rather than the other (unless the fibres converge, in which case the overall density of
adhesive fibres will be highest where they are coming together d adhesion measurements
in the blastocoel roof suggest that adhesion gradients are not present in amphibian
gastrulation).
GUIDANCE BY INHIBITION OF LOCOMOTION
As well as being guided by attractive molecules, cells can be repelled by contact with
molecules that interfere with the process of locomotion. This is most obvious in parts of
the embryo that must not be invaded. These areas are commonly marked by powerful
'keep out' signals. One such area is the posterior half-somite of vertebrates. Somites, the (indi-
rect) precursors of vertebrae and segmental musculature, form as a series of blocks each side
of the neural tube. The posterior half of the sclerotome (ventromedial part) of each somite
will form the hard parts of the vertebrae, where nerves must not run. The anterior part
will form the softer tissue through which spinal nerves should run, and in which the dorsal
root ganglia (relay stations that undertake pre-processing of sensory signals) should develop.
In the embryo, neural crest cells (progenitors of the dorsal root ganglia, amongst other things)
and axons travel only through the anterior half-somite and avoid entering the posterior half-
somite ( Figure 11.8 ).
The restriction of outgrowth to the anterior half-somites is known not be to an inherent
property of the neural tube because the pattern reverses if a somite is reversed ( Figure 11.9 ). 49
This suggests that the control lies in the somite itself. Furthermore, if the somites are removed
completely then axons emerge from all levels of the neural tube suggesting that the somites
work not by encouraging outgrowth at the anterior half but rather by repressing it in the
posterior half. Biochemical analysis of the somites has identified glycoproteins that are
expressed only in the posterior half-somite that, when applied to growth cones in culture,
cause them to cease advancing and to collapse so that they lose their whole leading edge
structure ( Figure 11.10 ). 50
Molecules that can cause collapse of the leading edges of neuronal growth cones and
migratory cells are widespread in the embryo. One of the best-studied families consists of
the Ephrins, which are important in many places. One of these places is the optic tectum,
the region of the brain that will receive axons coming from the eyes (as described in more