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BOX 3
DENDRITE FORMATION
Dendrites, the neuritic processes that are the main
receivers of synaptic input, are perhaps the most distinc-
tive features of neuronal morphology. Dendritic trees
differ from axonal arbors in a variety of ways; the most
obvious being that dendrites have more postsynaptic spe-
cializations while axons have more presynaptic special-
izations. Dendrites also grow somewhat differently
to axons (McAllister, 2000; Whitford et al., 2002). The
cytoskeleton of a dendrite is also different from that of an
axon, usually having a higher ratio of microtubules to
actin filaments and more rough endoplasmic reticulum
and polyribosomes. Axonal microtubules have their plus
ends pointed distally, while the dendritic microtubules
have a mixture of plus- and minus-ends leading. Micro-
tubule associated proteins are also differentially distrib-
uted in axons and dendrites. For example, MAP2 is
located in dendrites, while tau is located mainly in axons.
Treatment of cultured neurons with antisense constructs
that reduce MAP2 or tau expression have the expected
specific effects on the formation of dendrites or axons,
indicating that these proteins are particularly critical in
the formation or stabilization of these structures (Liu
et al., 1999; Yu et al., 2000). Certain membrane proteins
are also differentially distributed among axons and
dendrites; for instance, transmitter receptors are more
common on dendrites, whereas certain cell adhesion mol-
ecules and GAP-43 are found mainly on axons (Craig and
Banker, 1994). This polarity implies a sorting mechanism,
but the molecular basis of sorting different proteins to
different neuronal processes is not yet understood. The
initial polarity of neuronal cells in terms of axon versus
dendrite is not yet well understood, although current evi-
dence suggests that this polarity may be controlled by the
same cues, such as Par3, that specify polarity in epithelial
cells and asymmetric cell divisions (Shi et al., 2003).
Hippocampal cells in culture initially put out several
short neurites tipped with small growth cones (Figure
5.39). Initially, all of these processes are identical; for
example, they all have GAP-43 at their tips. Soon,
however, one of these processes begins to extend more
rapidly than the others, and as it does so it gathers axonal
specific markers so soon that only the axon has a GAP-43
tipped growth cone and the other processes begin to
assume dendrite specific markers. Interestingly, if the
emerging axon is selectively cut off, the longest of the
short processes starts to grow faster than the others and
it becomes the axon. Thus, neurons have an axon versus
dendrite polarity that is, to a certain extent, internally
regulated through a feedback mechanism by which
the axon inhibits the other neurites from assuming the
axonal identity they would attain by default (Goslin and
Banker, 1989). If at an early stage of polarization when
all processes are equal, the actin depolymerizing agent
cytochalasin is transiently applied locally to just one
neurite, that neurite will become the axon. If, however,
cytochalasin is applied uniformly to all the neurites, then
surprisingly they all become axons (Bradke and Dotti,
1999). This suggests that actin instability, possibly allow-
ing microtubule invasion, may be a key to the decision
of a process to become an axon or a dendrite. This model
is supported by direct manipulation of molecules
that control microtubule stabilization, such as collapsin
response mediator protein (CRMP-2, a MAP) and a GEF
FIGURE 5.39 In tissue culture, a hippocampal neuron begins
by putting out several minor processes that are basically equiv-
alent. One of these, the future axon, then begins to grow faster
than the other process and collects axon-specific components like
GAP43 and tau. After the axon has elongated, dendrites begin to
grow and express dendrite-specific components such as MAP2.
This figure shows three young hippocampal neurons in culture
stained for microtubules (red) and actin (green). At this stage, one
process is elongating while the shorter processes are not yet
definitive dendrites. If at this stage, the emerging axon is cut,
then a minor process, which would have otherwise become a
dendrite, begins to grow more rapidly and becomes the axon.
(From Ruthel and Hollenbeck, 2003)
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