In addition to their importance as a locus of disease, photoreceptor cells serve as an excellent model for studies in neuronal differentiation. Photoreceptor cells are highly polarized. At their apex, these neurons have a membranous outer segment, which contains proteins involved in the phototransduction cascade. Loss of function mutations in rhodopsin [29], or the structural protein, peripherin [30], result in an inability to form outer segments. At the other extremity, photoreceptors terminate with synaptic endings that make contact with the processes of horizontal and bipolar cells [31,32]. Rod spherules establish an invaginating synapse with rod bipolar dendrites and axonal endings of horizontal cells. This synapse is characterized by the presence of a ribbon in the presynaptic cytoplasm. Cone pedicles make invaginating synapses with the dendrites of on-cone bipolar cells and horizontal cells and basal junctions with the dendrites of off-cone bipolar cells. The factors regulating the formation of the photoreceptor synapses are completely unknown. At least one photoreceptor synaptic protein, HRG4, contains a potential Crx target sequence in its transcriptional regulatory sequence [33].