Introduction

The retina is one of the most highly conserved parts of the central nervous system (CNS), with unambiguous homology of major cell types among most chordates. These cells and their progenitors therefore share common patterns of gene activity. This widespread commonality is illustrated most dramatically by the Pax6 genes—a small family of transcription factors that trigger the formation of retinas, ommatidia, and photoreceptors in animals as diverse as fruit flies, squid, ascidians, fish, frogs, mice, and humans (Gehring and Ikeo, 1999; Onuma et al., 2002).

Retinas differ strikingly, however, in terms of the number and distribution of cells. Structural diversity of the vertebrate retina is generated using a relatively constant palette of cell types (Walls, 1942). Downstream effects mediated by transcription factors such as Pax6, and a rapidly expanding list of trophins, hormones, cytokines, and other signaling molecules, can produce significant changes in the number and ratio of cells and their interconnections. Evolution of the retina has therefore involved the episodic modulation of developmental processes that often adjust quantities, not quality.

The contrast between universal mechanisms and structural diversity highlights the need to study development using complementary approaches. The first approach focuses on fundamental qualitative features that are common denominators; the second approach focuses on quantitative adaptations of genetic networks that underlie functional and evolutionary transformations, as well as individual differences. This review is divided into sections that consider developmental, genetic, and functional factors that modulate the types and numbers of cells in the vertebrate retina from these two complementary viewpoints.

There are approximately 65 to 70 distinct cell types in the retina (Marc and Jones, 2002; Chapter 20, Retinal Neurotransmitters), each with its own idiosyncratic developmental history, and we only consider key themes and a few exemplar cell types. In Part 1, we cover the initial stages of visual system development, in which cell proliferation and differentiation produce the cellular substrates common to all vertebrate retinas. Most of our examples are drawn from studies of the South African clawed frog, Xenopus laevis, a long-favored experimental subject for developmental analyses. In Part 2, we consider the relation between cell number and visual system performance, addressing the question of how much variation is tolerated within species and why. Finally, we describe a novel approach called complex trait analysis that is being used to uncover the genetic basis of individual differences in retinal development. Combined developmental and genetic approaches should eventually provide a much better understanding of how evolutionary modifications have produced such amazing arrays of almost perfectly adapted eyes and retinas, a subject that gave Darwin serious pause (and a cold chill) a century and a half ago (Darwin, 1899; Dawkins, 1996).