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one unidentified factor known only because it binds a
particular plant lectin, known as VVA, which labels all
three retinorecipient layers, but none of the other layers
(Yamagata et al., 1995). To study the components of
lamina-specific termination in this system, sections of
formaldehyde-fixed tectum were put into a culture
dish with live retina. Amazingly, the retinal axons grow
into the correct layers in this situation. Yet if VVA is
added to this preparation, retinal axons become unable
to map to the correct laminae. Several different cad-
herin molecules, such as N-cadherin, R-cadherin, and
T-cadherin, are also expressed in different combina-
tions of the tectal laminae, with N-cadherin being selec-
tively present in the retinorecipient layers. Antibodies
to N-Cadherin when added to these cultures also cause
lamination errors, though of a different type, with some
axons stopping in the retinorecipient layers but not
extending in them. If BDNF is added to the in vitro
preparation, it does not affect the appropriate targeting
or retinal axons to the retinorecipient layers, but it does
cause excessive growth and branching in these layers.
These studies suggest that different molecules regulate
different aspects of laminar-specific innervation,
including recognition, innervation, and branching
(Sanes and Yamagata, 1999).
The retina is a multilayered structure, and the layers
where synapses occur, such as the inner plexiform
layer, are refined into functionally specialized sublam-
inae, such as the ON sublaminae that contain the
synaptic terminals of bipolar and amacrine cells that
fire when light is turned on and transmit this signal to
ON-type retinal ganglion cells whose dendrites are in
the same sublamina, and the OFF sublamina that does
the same for lights off. Sidekick 1 (Sdk-1) and Sidekick
2 (Sdk-2), have been identified as sublamina-specific
molecules within the inner plexiform layer (Yamagata
et al., 2002). Sdks are homophilic CAMs of the IgG
superfamily, and each Sdk is expressed by the pre-
synaptic terminals of a subset of bipolar and amacrine
cells and the postsynaptic dendrites of a subset of gan-
glion cells that project to a common sublamina. Ectopic
expression of Sdk-1 in Sdk-negative cells redirects their
processes to the Sdk-1 positive sublamina, and similar
experiments with Sdk-2 show that it directs processes
to the Sdk-2 sublamina (Figure 6.23). Retinal ganglion
cells, although they express Sdks, are not absolutely
critical for the formation of these sublaminae. As in the
zebrafish mutant lak , ganglion cells are never born, and
yet the ON and OFF sublaminae form, though in a
delayed and slightly disarrayed way (Kay et al., 2004).
That homophilic adhesion molecules bind axonal ter-
minals to the dendritic processes of cells that are des-
tined to synapse onto each other makes a good deal of
sense. As we will see in the next section, this kind of
process is used a great deal when we consider targeting
at the cellular or synaptic level.
The final step in targeting comes when axonal ter-
minals actually make contact with the specific cells or
parts of cells with which they will synapse. Choosing
a specific postsynaptic partner is aided by getting the
terminal branches to the right topographic and
laminar position, but the next stage involves the actual
adhesion of specific terminals to specific postsynaptic
target cells. A good example of how individual axons
choose particular target cells is the neuromuscular
system of the Drosophila larva. In each segment of the
FIGURE 6.23 Sidekicks in sublaminar targeting. In the inner plexiform layer in the retina, neurons
expressing the same sidekick send processes to the same sublamina, thereby establishing lamina-specific
synaptic connections. Overexpression of a sidekick shifts connectivity. (After Yamagata et al., 2003)
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