Guidance by Contact - Mechanisms of Morphogenesis - page 125

It is interesting to note that adhesive surfaces need not be continuous in order to support
axon growth. Spaced spots of highly adhesive substrates can allow axons to extend over
intervening substrates of very low adhesion as long as the spots are close enough together
to be explored by filopodia of growth cones on adjacent spots. 7 This may be highly relevant
to the phenomenon of waypoint navigation (see Chapter 12).
If the only possible activity of adhesion complexes were to be the transmission of mechan-
ical forces, the case for haptotaxis as a navigational mechanism could be made simply from
the observations described above. Integrin-containing adhesion complexes can do much
more than transduce force, however; in particular they can trigger signal transduction path-
ways via junction-associated molecules such as FAK, Rho and Src. Indeed, most types of
adhesion complex are associated with some kind of signalling system. This makes guidance
directly by haptotaxis difficult to disentangle experimentally from guidance by ligand-
receptor signalling.
The key difference between haptotaxis and biochemical substrate-sensing is that, while
they both require binding between the cell and extracellular ligands, only the haptotaxis
mechanism would require those ligands to be capable of exerting mechanical forces. This
fact has been used in an elegant study on the steering of growth cones that demonstrates
unequivocally that, at least in one model system, simple ligand-receptor binding is not
enough and that physical forces are required. Bag cells of the gastropod sea-slug Aplysia
californica are endowed with very large growth cones that bear a homophilic adhesion
molecule of the NCAM superfamily, called 'apCAM'. Small beads coated either with apCAM,
or with antibodies against it, bind the apCAM on the growth cone surface. Once bound, the
beads are swept back with the general retrograde flow of actin showing that they are cross-
linked to the cytoskeleton. Under these conditions, the presence of the beads has little effect
on the direction of cell movement, showing that the simple act of binding and clustering
apCAM, and triggering whatever biochemical changes may follow from this, is not itself suffi-
cient to guide growth cones. The rearwardmotion of bound beads can, however, be prevented
by physically blocking their progress with a fine glass needle ( Figure 11.6 ). This effectively
FIGURE 11.6 Haptotaxis caused by restraining the movement of beads adhering to the apCAM adhesion
complex of A. californica 's bag cell growth cones.