53: Differentiation and Survival of Nerve Cells

Introduction

• The Proliferation of Neural Progenitor Cells Involves Symmetric and Asymmetric Modes of Cell Division

• Radial Glial Cells Serve As Neural Progenitors and Structural Scaffolds

• The Generation of Neurons or Glial Cells Is Regulated by Delta-Notch Signaling and Basic Helix-Loop-Helix Transcription Factors

• Neuronal Migration Establishes the Layered Organization of the Cerebral Cortex

• Central Neurons Migrate Along Glial Cells and Axons to Reach Their Final Settling Position

  • Glial Cells Serve As a Scaffold in Radial Migration

  • Axon Tracts Serve As a Scaffold for Tangential Migration

  • Neural Crest Cell Migration in the Peripheral Nervous System Does Not Rely on Scaffolding

• The Neurotransmitter Phenotype of a Neuron Is Plastic

  • The Transmitter Phenotype of a Peripheral Neuron Is Influenced by Signals from the Neuronal Target

  • The Transmitter Phenotype of a Central Neuron Is Controlled by Transcription Factors

• The Survival of a Neuron Is Regulated by Neurotrophic Signals from the Neuron's Target

  • The Neurotrophic Factor Hypothesis Was Confirmed by the Discovery of Nerve Growth Factor

  • Neurotrophins Are the Best Studied Neurotrophic Factors

  • Neurotrophic Factors Suppress a Latent Death Program in Cells

• An Overall View

In the preceding chapter we described how local inductive signals pattern the neural tube and establish the early regional subdivisions of the nervous system—the spinal cord, hindbrain, midbrain, and forebrain. Here we turn to the issue of how progenitor cells within these regions differentiate into neurons and glial cells, the two major cell types that populate the nervous system.

We discuss some of the molecules that specify neuronal and glial cell fates and how they are regulated. The basic mechanisms of neurogenesis endow cells with common neuronal properties, features that are largely independent of the region of the nervous system in which they are generated or the specific functions they perform. We also discuss the mechanisms by which developing neurons express neurotransmitters and synaptic receptors.

After the identity and functional properties of the neuron have begun to emerge, additional developmental processes determine whether the neuron will live or die. Remarkably, approximately half of the neurons generated in the mammalian nervous system are lost through programmed cell death. We examine the factors that regulate the survival of neurons and the possible benefits of widespread neuronal loss. Finally, we describe the existence of a core biochemical pathway that programs the death of nerve cells.

The Proliferation of Neural Progenitor Cells Involves Symmetric and Asymmetric Modes of Cell Division

The mature brain comprises billions of nerve cells and even more glial cells. Yet its precursor, the neural plate, initially comprises only a few hundred cells. From this simple comparison we infer that regulation of the proliferation of neural cells is a major driving force in shaping brain development. Histologists in the late 19th century showed that neural epithelial cells close to the ventricular lumen of the embryonic brain exhibit features of mitosis, and we now know that the proliferative ...