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Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001.

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Neuroscience. 2nd edition.

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Neuronal Migration

The cellular positioning that constrains local signaling depends on migration of postmitotic neuroblasts in the fetal brain. Migration is a ubiquitous feature of development that brings cells into appropriate spatial relationships. In the nervous system, migration during development brings different classes of neurons together so that they can interact appropriately. The final location of a postmitotic nerve cell is perhaps even more critical than the positioning of non-neural cells, because neural function depends on precise connections made by neurons and their targets. In short, the developing presynaptic and postsynaptic elements must be in the right place at the right time.

After their final mitosis in the ventricular zone, most neuroblasts migrate substantial distances. For neurons of the central nervous system, this migration remains within the limits of the neural tube. However, neurons of the peripheral nervous system, which come from the neural crest, arise from cells that have often had a long journey through several embryonic enviroments (see Figure 22.2). Even within the central nervous system, the significant distances traversed are especially obvious in large animals like primates. To form the cerebral cortex, for example, neurons must sometimes travel several millimeters from the ventricular zone to the pial surface.

Much is now known about the mechanics of how neurons move from their birthplace to their final destination. Depending on the area of the developing nervous system in which they originate, migrating neurons follow one of two strategies. Neural crest cells are largely guided along distinct migratory pathways by specialized adhesion molecules in the extracellular matrix or by molecules on the surfaces of cells in the embryonic periphery (see Figure 22.2). At different developmental stages, similar molecules are probably used to guide axonal outgrowth (see Chapter 23). In contrast, neurons in many regions, including the cerebral cortex, cerebellum, hippocampus, and spinal cord, are guided to their final destinations by crawling along a particular type of glial cell, called radial glia, which acts as a cellular guide (Figure 22.11).

Figure 22.11. Radial migration in the developing cortex.

Figure 22.11

Radial migration in the developing cortex. (A) Section through the developing forebrain showing radial glial processes from the ventricular to the surfaces. Micrograph shows migrating neurons labeled with an antibody to neuregulin, specific for migrating (more...)

Histological observations of embryonic brains made by Wilhelm His and Ramon y Cajál during the early years of the nineteenth century had suggested that neuroblasts crawled along glial guides to their final locations (Figure 22.11A). This observation was supported by analyses of electron microscopic images of fixed tissue in the 1960s and 1970s (Figure 22.11B,C), and indeed by the orderly relationship between birthdates and final position of distinct cell types in the cerebellum and cerebral cortex (see Figure 22.7 and Box D). Subsequently, innovations in cell culture techniques and light microscopy made it possible to observe this process of migration directly. When radial glial cells and immature neurons are isolated from the developing cerebellum or cerebral cortex and mixed together in vitro, the neurons attach to the glial cells, assume the characteristic shape of migrating cells seen in vivo, and begin moving along the glial processes. Indeed, the membranes of glial cells, when coated onto thin glass fibers, support normal migration. Several cell surface adhesion molecules, extracellular matrix adhesion molecules, and associated signal transduction molecules apparently mediate this process (Figure 22.11). Although in many regions of the brain—particularly those that give rise to nuclear cell groups—neurons migrate without the benefit of glial guides, migration along radial glial fibers is always seen in regions where cells are organized into layers, like the cerebral cortex, hippocampus, and cerebellum. Both neuropathological observations and more recent molecular and genetic studies indicate that some forms of mental retardation, epilepsy, and other neurological problems arise from the abnormal migration of cerebral cortical neurons (see also Box B in Chapter 19).

Relatively little is known about the specific messages that neurons receive as they migrate in the central nervous system. It is apparent, however, that moving through a changing cellular environment has important effects on the differentiation of neurons. Such effects are most thoroughly documented in the migration of neural crest cells, where the migratory paths of precursor cells are related to both the ultimate position in the body and neuronal identity. The distinct signals along these pathways can be secreted molecules (including some of the peptide hormones used at earlier times for neural induction), cell surface ligands and receptors (adhesion molecules and other signals), or extracellular matrix molecules (see Chapter 23). These signals are made available from somites, visceral epithelial structures (like the developing dorsal aorta), mesodermally derived mesenchymal cells, and the neural crest cells themselves. Of particular significance is the fact that specific peptide hormone growth factors cause neural crest cells to differentiate into distinct phenotypes (Figure 22.12). These effects depend on the location of the neuronal precursor cell along a migratory pathway, different signals being available at different points. Such position-dependent cues are probably not restricted to the peripheral nervous system; in the cerebellum, for example, different patterns of genes are expressed in migrating granule neurons at different locations, implying the existence of different signals (as yet unknown) along the migratory path.

Figure 22.12. Cell signaling during the migration of neural crest cells.

Figure 22.12

Cell signaling during the migration of neural crest cells. The establishment of each precursor type relies on signals provided by one of several specific peptide hormones. The availability of each signal depends on the migratory pathway.

Thus, neuronal migration involves much more than the mechanics of moving cells from one place to another. As is the case for inductive events during the initial formation of the nervous system, stereotyped movements bring different classes of cells into contact with one another, thereby providing a means of constraining cell-cell signaling to specific times and places.

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By agreement with the publisher, this book is accessible by the search feature, but cannot be browsed.

Copyright © 2001, Sinauer Associates, Inc.
Bookshelf ID: NBK10831

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