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Chapter 23 Summary

Neurons in the developing brain must integrate a variety of signals to determine where to send their axons, what cells to form synapses upon, how many synapses to make and retain, and whether to live or die. A remarkable transient cellular specialization, the growth cone, is responsible for axon growth and guidance. Growth cones explore the embryonic environment and determine the direction of axon growth as well as recognizing appropriate targets. Their motile properties allow growth cones to approach, select, or avoid a target according to modulation of the actin and microtubule cytoskeleton by numerous signaling mechanisms, many of which involve changes in intracellular Ca2+. The instructions that elicit growth cone responses come from adhesive, chemotropic, chemorepulsive, and trophic molecules. These molecules are embedded in the extracellular matrix, found on cell surfaces, or secreted into extracellular spaces. Their cues ensure that coherent axon pathways are formed and prevent inappropriate connections. Adhesive, attractive, and repulsive molecules also influence the differentiation of growth cones into synapses. Further signals are transmitted by neurotrophins, molecules made by neuronal targets in small quantities that bind to a variety of receptors to elicit distinct cellular responses. Neurotrophic influences— cell survival or death, process growth, and modulation of synaptic activity—help determine which neurons remain in a neural circuit, how they are connected, and how they continue to change. Defects in the early guidance of axons or subsequent trophic regulation of synaptogenesis have been implicated in a variety of congenital neurological syndromes and developmental disorders, and neurotrophic dysfunction in the adult CNS may underlie degenerative pathologies such as Alzheimer’s and Parkinson’s diseases.