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Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

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NEURAL DEVELOPMENT

1209

motor

neuron

generation

2.5 day chick

embryo

developing

spinal cord

9 day chick

embryo

motor

neuron

death

section of spinal cord

Figure 21–81 The survival of motor

neurons depends on signals provided

by the target muscles. (A) Removal of

the limb bud shortly after arrival of motor

axons results in the death of motor neurons

in the spinal cord on the amputated side.

(B) Transplantation of an extra limb bud

increases the survival of motor neurons.

(After E. Kandel et al., Principles of Neural

Science, 5th ed., New York: McGraw Hill

Medical, 2012.)

(A)

REMOVAL OF

ONE DEVELOPING

LIMB BUD

missing limb

10% survive

normal limb

50% survive

section of spinal cord

developing

spinal cord

motor

neuron

generation

motor

neuron

death

(B)

TRANSPLANTATION

OF EXTRA

LIMB BUD

extra limb

75% survive

normal limb

50% survive

NGF is produced by the tissues that these neurons innervate. When extra NGF is

provided, extra sensory and sympathetic neurons survive, just as if extra target

tissue were present. Conversely, in a mouse with a mutation that inactivates the

gene for NGF or for its receptor MBoC6 n22.239/22.82

(a receptor tyrosine kinase called TrkA), almost

all sympathetic neurons and the NGF-dependent sensory neurons are lost. There

are many neurotrophic factors, only a few of which belong to the neurotrophin

family, and they act in different combinations to promote the survival and growth

of different classes of neurons.

Formation of Synapses Depends on Two-Way Communication

Between Neurons and Their Target Cells

At journey’s end, the task of a growth cone is to halt its travels and make synapses

with specific target cells. Synapses were introduced in Chapter 11, where we discussed

channels and the electrical properties of membranes. Two main classes

of synapses are found in vertebrates; those made with muscle cells and those

made with other neurons. Synapse formation is best understood in the case of

the highly specialized connections between motor neurons and skeletal muscle

cells—so-called neuromuscular junctions (see Figure 11–38). During synapse

formation, the axonal growth cone differentiates into a nerve terminal that contains

synaptic vesicles filled with the neurotransmitter acetylcholine, while acetylcholine

receptors become clustered in the muscle cell plasma membrane at

the site of synapse formation. A synaptic cleft separates the pre- and postsynaptic

plasma membranes, and a thin sheet of basal lamina lies in this space between

them (Figure 21–82).

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