114
Brain Development
from the retinal neurons at the ectopic
position could Fnally reach the original po-
sition, indicating that the axon pathFnding
events are totally dependent on various en-
vironmental cues (
ChemoafFnity hypothe-
sis
). Landmesser and colleagues also found
that if the spinal cord at the limb level is
rotated by 180
along the A–P axis in
chicken embryos, the motor axons orig-
inating from the ectopic position could
Fnally reach the normal muscle target.
To sense such various environmental
cues, the tip of the axon is special-
ized into a structure called
growth cone
(±ig. 10a). During axon guidance, growth
cones appear to contact either supporting
cells or previously established nerve tracts
from other neurons. Those cells harbor-
ing the activity to guide growth cones are
named
guidepost/stepping-stone cells
and
pi-
oneer neurons
respectively (±ig. 10a). Once
a growth cone arrives at a target region,
i
ts
topsandformsas
tab
lejunc
t
ionw
i
th
the target neuron, the maturated form of
which is termed synapse. The neural cir-
cuitsatthispointare,however,premature
and sometimes contain wrong connec-
tions. ±or instance, while only a single
climbing Fber innervates each Purkinje
neuron in the adult mouse cerebellum,
multiple innervations were found at peri-
natal stages. Such wrong connections are
eliminated in an activity dependent man-
ner. In the mammalian visual cortex,
inputs from the right eye compete with
thosefromthelefteyetomaketheocu
lar
dominance column. In this process, inputs
from both eyes have been shown to occupy
the same area at the initial step of the devel-
opment but eventually lose the connection
to form the ocular dominance column.
Elimination of inputs from one eye during
the initial stages resulted in the loss of the
ocular dominance column, indicating that
this process was also activity dependent.
Even in the adult brain, neuronal circuits
are always modiFed over time mainly by
changing the synaptic junctions in number
and strength.
6
Molecular Aspects to Wire up the Nerve
Cells into Functional Circuits
There are mainly two mechanisms to ex-
plain axon guidance; one is a contact
dependent and the other is a contact-
independent machinery. In the former,
interaction between the transmembrane
and/or membrane-bound receptor in the
growth cone and its ligands exists on the
neighboring cell membrane or extracel-
lular matrix (ECM) and plays a major
role, while secreted molecules from re-
mote positions and their receptors on the
membrane of growth cones are involved
inthela
t
ter
.Thefo
l
low
inga
reexamp
les
of these two mechanisms:
Fig. 10
Mechanisms involved in axon guidance. (a) A schematic drawing explaining how a growth
cone can be guided to the target area. For details, see text, (b) The retino-tectum connection system
in chicken. Visual information is precisely represented in the tectum because of the topographic
connection pattern. In order to establish such a connection pattern, the graded expression of the Eph
receptor in the retina and that of its ligand ephrin in the tectum appear to play an important role,
(c) A commissural interneuron in the spinal cord can express different sets of molecules along the
axon in response to various environmental cues. (d) Secreted molecule Slit mediated axon guidance
in the
Drosophila
embryo is strictly regulated by the posttranscriptional modi±cation of the Slit
receptor Robo. The midline glia is the source of the chemorepellant, Slit.
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