54: The Growth and Guidance of Axons

Introduction

• Differences in the Molecular Properties of Axons and Dendrites Emerge Early in Development

  • Neuronal Polarity Is Established Through Rearrangements of the Cytoskeleton

  • Dendrites Are Patterned by Intrinsic and Extrinsic Factors

• The Growth Cone Is a Sensory Transducer and a Motor Structure

• Molecular Cues Guide Axons to Their Targets

• The Growth of Retinal Ganglion Axons Is Oriented in a Series of Discrete Steps

  • Growth Cones Diverge at the Optic Chiasm

  • Ephrins Provide Gradients of Inhibitory Signals in the Brain

• Axons from Some Spinal Neurons Cross the Midline

  • Netrins Direct Developing Commissural Axons Across the Midline

  • Chemoattractant and Chemorepellent Factors Pattern the Midline

• An Overall View

In the two preceding chapters we saw how neurons are generated in appropriate numbers, at correct times, and in the right places. These early developmental steps set the stage for later events that direct neurons to form functional connections with target cells. To form connections neurons have to extend long processes—axons and dendrites—which permit connectivity with postsynaptic cells and synaptic input from other neurons.

The growing axon may have to travel a long distance—up to several meters in a giraffe—and ignore many inappropriate neuronal partners before terminating in just the right region and recognizing its correct synaptic targets. In this chapter we examine how neurons elaborate axons and dendrites, and how axons are guided to their targets. In subsequent chapters we consider how neurons form synapses and how patterns of connections are shaped by activity.

We begin this chapter by discussing how certain neuronal processes become axons and others dendrites. We then consider the challenges that face an axon as it projects along tortuous pathways to its target. Finally, we illustrate general features of axonal guidance by describing the development of two well-studied axonal pathways: one that conveys visual information from the retina to the brain and another that conveys cutaneous sensory information from the spinal cord to the brain.

Differences in the Molecular Properties of Axons and Dendrites Emerge Early in Development

The processes of neurons vary enormously in their length, thickness, branching pattern, and molecular architecture. Nonetheless, most neuronal processes fit two functional categories: axons and dendrites. More than a century ago Santiago Ramón y Cajal hypothesized that this distinction underlies the ability of neurons to transmit information in a particular direction, an idea he formalized as the law of dynamic polarization. Cajal wrote that "the transmission of the nerve impulse is always from the dendritic branches and the cell body to the axon." In the decades before electrophysiological methods were up to the task, this law provided a means of analyzing neural circuits histologically. Although exceptions have been found, Ramón y Cajal's law remains a basic principle that relates structure and function in the nervous system and highlights the importance of knowing how neurons acquire their polarized form.

Neuronal Polarity Is Established Through ...