52: Patterning the Nervous System

Introduction

• The Neural Tube Becomes Regionalized Early in Embryogenesis

• Secreted Signals Promote Neural Cell Fate

  • Development of the Neural Plate Is Induced by Signals from the Organizer Region

  • Neural Induction Is Mediated by Peptide Growth Factors and Their Inhibitors

• Rostrocaudal Patterning of the Neural Tube Involves Signaling Gradients and Secondary Organizing Centers

  • Signals from the Mesoderm and Endoderm Define the Rostrocaudal Pattern of the Neural Plate

  • Signals from Organizing Centers within the Neural Tube Pattern the Forebrain, Midbrain, and Hindbrain

• Dorsoventral Patterning of the Neural Tube Involves Similar Mechanisms at Different Rostrocaudal Levels

  • The Ventral Neural Tube Is Patterned by Sonic Hedgehog Protein Secreted from the Notochord and Floor Plate

  • The Dorsal Neural Tube Is Patterned by Bone Morphogenetic Proteins

  • Dorsoventral Patterning Mechanisms Are Conserved Along the Rostrocaudal Extent of the Neural Tube

• Local Signals Determine Functional Subclasses of Neurons

  • Rostrocaudal Position Is a Major Determinant of Motor Neuron Subtype

  • Local Signals and Transcriptional Circuits Further Diversify Motor Neuron Subtypes

• The Developing Forebrain Is Patterned by Intrinsic and Extrinsic Influences

  • Inductive Signals and Transcription Factor Gradients Establish Regional Differentiation

  • Afferent Inputs Also Contribute to Regionalization

• An Overall View

Avast array of neurons and glial cells is produced during development of the vertebrate nervous system. Different neurons develop in discrete anatomical positions, acquire varied morphological forms, and establish connections with specific populations of target cells. The diversity of neurons is far greater than that of cells in any other organ of the body. The retina, for example, has dozens of classes of amacrine interneurons, and the spinal cord more than a hundred motor neuron classes. Nevertheless, the true number of neuronal classes in the mammalian central nervous system remains unclear—perhaps more than a thousand.

The diversity of neuronal cell types underlies the impressive computational properties of the mammalian nervous system. Yet, as we describe in this chapter and those that follow, the developmental principles that drive the differentiation of the nervous system are begged and borrowed from those used to direct the development in other tissues. In one sense the development of the nervous system merely represents an elaborate example of the basic challenge that pervades all of developmental biology: How to convert a single cell, the fertilized egg, into the highly differentiated cell types that characterize the mature organism.

Indeed, the convergence of developmental biology and neural science has led us to appreciate that superficial differences in the structure of the nervous systems of diverse species belie the expression of commonly shared principles and mechanisms of neural development that have been conserved throughout evolution. Much of what we know about the cellular and molecular bases of neural development in vertebrates comes from genetic studies of so-called simple organisms, most notably the fruit fly Drosophila melanogaster and the worm Caenorhabditis elegans.

Nevertheless, because the eventual goal of studies of neural development is surely to explain how the assembly of the ...