Biology Reference
In-Depth Information
although it reappears on aggregation, showing that the disaggregation process itself did not
destroy the receptor. Even the contact between three cells is sufficient to restore chemotaxis.
Isolated cells, with no contact, are still motile but they push out leading edge protrusions in
random directions. The distribution of Rac (which activates lamellipodium formation, see
Chapter 8) in these cells is not polarized. It is also not polarized in the bulk cells of a collective,
but it is strongly polarized in the outer cells, which are the only cells to experience the asym-
metry of having neighbours behind them although not in front. Significantly, in most of these
outer cells, the polarization of Rac is aligned with the contact-free axis and not with the Sdf1
gradient (in some cells, facing directly towards Sdf1, the two alignments coincide). The
stability of protrusions does, however, depend on Sdf1. These data together suggest a model
in which cell contacts direct protrusive activity to the outer parts of the outer cells of the
group, but the protrusions have greatest persistence, and therefore greatest total effect,
when they happen to extend towards the chemoattractant. The system therefore uses both
space and time to achieve efficient chemotaxis.
CA
SE STUDY: THE ROSTRAL MIGRATORY STREA
M
The rostral migratory stream is a movement of neuroblasts (neuronal precursor cells)
through the brains of rodents and it is unusual, for a neuro-developmental event, in that it
takes place throughout life (at least in rodents).
14
Created in the subventricular zone of the
forebrain, these cells migrate to the olfactory bulb where they differentiate to become inter-
neurons. During their migration, which covers about 500 cell diameters even in the mouse,
these cells move as a connected chain of cells: the rostral migratory stream.
15
The neurons
move at high speed (20
e
30
m/hr), though tube-like pathways bound by astrocytes,
16
and
seem to navigate both by contact cues and by long-range signalling, using molecules such
as Netrin, GDNF, BDNF and HGF from their targets.
17
The tendency of the cells to form
chains is strong enough for it to take place in culture too. When placed in Matrigel, explants
of subventricular zones emit long, connected chains of neuronal precursors.
18
The cells them-
selves are highly motile with active growth cones and, scrambling on one another, they
frequently change positions, overtaking and being overtaken.
The migrating cells show the presence of adherens-like junctions with one another, by elec-
tron microscopy
19
and express the homophilic cell-cell adhesion and signalling molecule,
NCAM. Mice deficient in NCAM show defective migration and this gives initial hope that
the explanation for chain formation would be relatively straightforward and would use
homophilic adhesion via NCAM. Transplantation experiments, however, showed that
NCAM mutant cells could migrate properly in a wild-type environment but wild-type cells
could not migrate properly in a mutant environment; this suggests that the NCAM is needed
for the environment rather than for chain-making interactions between the migrating cells
themselves.
20
Migrating neuroblasts also express Girdin at their cell-cell junctions; without
this protein, the cell-cell junctions cannot be detected
d
neuroblasts fail to form chains and
instead migrate individually and inefficiently both in vivo and in culture.
20
The precise
biochemical function of Girdin in this context is unclear at the time of writing (the interaction
partners that are important in other systems seem irrelevant in the rostral migratory stream),
although it should be known soon.
m
