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Motor axons travel in parallel through a cranial nerve in a mouse. The Brainbow neuroimaging technique used to create this image permits labeling of individual neurons with distinct colors. The method has advanced dramatically our ability to map and visualize neurons in the living brain. (Reproduced, with permission, from Joshua Sanes. Image appeared in Livet J, Weissman TA, Kang H, Draft RW, Lu J, Bennis RA, Sanes JR, Lichtman JW. Nature 2007; 540:56-61)

All of the innumerable behaviors controlled by the mature nervous system—from the perception of sensory input and the control of motor output to cognitive functions such as learning and memory—depend on precise interconnections formed by many millions of neurons during embryonic and postnatal development.

More than a century ago, Santiago Ramón y Cajal undertook a comprehensive series of anatomical studies on the structure and organization of the nervous system, and then set out to probe its development. Modern developmental neuroscientists follow in Ramón y Cajal's footsteps, trying to uncover the processes underlying the formation of neural circuits. In the intervening years technical advances have made it possible to extend this inquiry to the molecular and genetic levels. During the past few decades there have been many striking advances in understanding the molecular basis of neural development. These advances include the identification of proteins that determine how nerve cells acquire their identities, how they extend axons to target cells, form synaptic connections, and have also provided insight into how synaptic connections are modified by experience.

Development of the nervous system depends on the expression of particular genes at particular times and places. This spatial and temporal pattern of gene expression is regulated by both hardwired molecular programs and epigenetic processes. The factors that control neuronal differentiation originate both from cellular sources within the embryo and from the external environment. Internal influences include cell surface and secreted molecules that control the fate of neighboring cells, as well as transcription factors that act at the level of DNA to control gene expression. External factors include nutrients, sensory stimuli, and social experience, the effects of which are mediated through patterned changes in the activity of nerve cells. The interaction of these intrinsic and environmental factors is critical for the proper differentiation of each nerve cell.

The recent progress in defining the mechanisms that control the development of the nervous system is due largely to molecular biological studies of neural function. To take but one example, the molecular cloning of genes encoding extrinsic factors (eg, secreted proteins) and intrinsic determinants (eg, transcription factors) has provided unanticipated insight into the differentiation of the nervous system. Moreover, the function of specific genes can now be tested directly in transgenic animals or in animals in which individual genes have been inactivated by mutation.

Other important advances have emerged from the analysis of simple and genetically accessible organisms such ...

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