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The Questions of Developmental Biology

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Each neurotrophin can promote the growth <strong>of</strong> some<br />

axons to its source while inhibiting other axons. For instance,<br />

BDNF can stop the growth <strong>of</strong> certain sensory neurons from the<br />

rat dorsal root ganglia, and these same neurons can be induced<br />

to turn toward a source <strong>of</strong> NT-3 (Figure 13.24).<br />

Although genetic and biochemical techniques enable us<br />

to look at the effect <strong>of</strong> one type <strong>of</strong> molecule at a time, we must<br />

remember that any growth cone is sensing a wide range <strong>of</strong><br />

chemotactic and chemorepulsive molecules, both in solution<br />

and on the substratum upon which it migrates. Growth cones do not rely on a single type <strong>of</strong><br />

molecule to recognize their target. Rather, they integrate the simultaneously presented attractive<br />

and repulsive cues and select their targets based on the combined input <strong>of</strong> these multiple cues<br />

(Winberg et al. 1998).<br />

Address selection:<br />

activitydependent<br />

development<br />

When an axon<br />

contacts its target (usually<br />

either a muscle or another<br />

neuron), it forms a<br />

specialized junction called a<br />

synapse. Neurotrans-mitters<br />

from the axon terminal are<br />

released at these synapses<br />

to depolarize or<br />

hyperpolarize the<br />

membrane <strong>of</strong> the target cell<br />

across the synaptic cleft.<br />

<strong>The</strong> construction <strong>of</strong><br />

the synapse involves<br />

several steps (Figure 13.25;<br />

Burden 1998). When motor<br />

neurons in the spinal cord<br />

extend axons to muscles,<br />

growth cones that contact newly formed muscle cells migrate over<br />

their surfaces. When the growth cone first adheres to the muscle<br />

cell membrane, no specializations can be seen in either membrane.<br />

However, the axon terminals soon begin to accumulate<br />

neurotransmitter-containing synaptic vesicles, the membranes <strong>of</strong><br />

both cells thicken at the region <strong>of</strong> contact, and the synaptic cleft<br />

between the cells fills with extracellular matrix that includes a<br />

specific form <strong>of</strong> laminin. This muscle-derived laminin specifically<br />

binds the growth cones <strong>of</strong> motor neurons and may act as a "stop<br />

signal" for axonal growth (Martin et al. 1995; Noakes et al. 1995).<br />

In at least some neuron-to-neuron synapses, the synapse is<br />

stabilized by N-cadherin.

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