Biology Reference
In-Depth Information
1993). PSA may affect migration in the RMS by reducing the adhesiveness of
N-CAM molecules; however, this effect of PSA cannot explain how cells
migrate actively and unidirectionally toward the olfactory bulb. In addition,
in mice deficient in N-CAM, migration in the RMS is only partially
diminished (Chazal et al., 2000) suggesting that other molecules contribute to
the directed migration in this pathway.
To identify other molecules that regulate RMS migration, we developed a
slice culture system that allows us to image the migrating cells at high
temporal and spatial resolution in the presence and absence of function-
blocking antibodies against integrins and other putative adhesion or guidance
molecules (Murase and Horwitz, 2002; Webb et al., 2002). We prepared
200 mm thick slices from the forebrains of postnatal mice and labelled the
migrating neuronal precursors with DiI crystals. In migrating cells, we
observed a single, long and persistent leading process orientated in the
direction of migration (Figure 19.4). In contrast to the somitic cells, the
neuronal precursors migrated along a highly constrained pathway; the average
rate of migration was about 100 mm/h. When the slices were treated with
function blocking integrin antibodies against a1, b1orav at the stage of
development in which the integrins were expressed, migration was inhibited.
This suggests a role for integrins in the migration of neuronal precursors in the
RMS.
Since the netrin family and their receptors are emerging as key molecules in
guiding growing axons to their targets and directing cell migration during
neural development, we asked whether the netrin-1 receptor, Deleted in
Colorectal Carcinoma (DCC), played a role in RMS migration. When we
incubated the brain slices with function blocking DCC antibodies, migration
was no longer unidirectional. These cells continued to extend a single, long
protrusion but it retracted frequently and was not directionally polarized. This
suggests that DCC, possibly through an interaction with netrin-1, contributes
to the formation of directed protrusions and migration of the neural
precursors along a defined pathway. While both integrins and DCC appear
to regulate migration in the RMS, these molecules have distinct functions.
DCC is involved in directional, but not random, migration of the neural
precursors in the RMS whereas integrin ligation is essential for any movement
of these cells.
Conclusions
It is now apparent that the biological systems and imaging technology are
available for studying cell migration in situ. While others have studied
migration in similar systems, the focus has been on the migration pathways
and guidance. The new focus is on using these systems to study the dynamics
