For well over a century, the retina has been a favorite model system for experimental studies of the central neurous system (CNS). Anatomical studies, including the pioneering studies of Ramon y Cajal, have identified the ordered laminar arrangement of the five neuronal and two glial cell types, as well as the numerous subclasses of each cell type (see Chapter 20). The retina has also been used extensively by experimental embryologists, and we now have a detailed description of how many of the cell types of the retina are formed from a sheet of primitive neuroepithelium. Such a rich background of information has made it possible for more recent biochemical studies to explain many of these events in molecular terms.

In the plane of the retina, many cell types form a mosaic whose spacing and connectivity patterns vary with position. Retinal position also dictates the topographical connectivity of ganglion cell terminals. Here too, classical anatomical and physiological studies have defined the timing and specificity of this connectivity, and recent studies in the retina have now begun to suggest molecular pathways by which positional specification might be effected.

This chapter will discuss the major steps of retinal development in molecular terms. In particular, it will try to show that several general principles govern many steps of development. First, many developmental steps consist of transcriptional changes in response to one or more mor-phogenetic gradients in the concentration of diffusible factors (usually peptides). Second, transcription factors that delineate tissue compartments often reciprocally inhibit transcription factors in adjacent compartments. As described later, a combination of these two principles leads to the formation of sharp boundaries. Third, the same families of molecules, even the same molecules, are used at multiple stages of development. This has the experimental advantage that understanding how one retinal cell type is formed can provide many clues about the mechanisms involved in the formation of other retinal cell types.

While our understanding of the molecular mechanism of retinal development has advanced dramatically in recent years, we probably have only the crudest outline of the whole process. Nevertheless, this outline seems to be robust, and new information is likely to expand, not replace, out current view.

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