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The Journal of Neuroscience, January 26, 2005, 25(4):941-949; doi:10.1523/JNEUROSCI.4657-04.2005

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Development/Plasticity/Repair
Two ribeye Genes in Teleosts: The Role of Ribeye in Ribbon Formation and Bipolar Cell Development

Lei Wan, Wolfhard Almers, and Wenbiao Chen

Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239

Ribeye is the only known protein specific to synaptic ribbon, but its function is unclear. We show that the teleost fish, Fugu and zebrafish, have two ribeye genes, ribeye a and ribeye b. Whole-mount in situ hybridization revealed that ribeye a is expressed in tissues containing synaptic ribbons, including the pineal gland, inner ear, and retina. Ribeye b is absent in the pineal gland. In the retina, ribeye a is expressed in both photoreceptors and bipolar cells, whereas ribeye b is detected only in photoreceptors. To study the function of Ribeye a in retina, we depleted it by morpholino antisense oligos. Fish deficient in Ribeye a lack an optokinetic response and have shorter synaptic ribbons in photoreceptors and fewer synaptic ribbons in bipolar cells. Their bipolar cells still target Syntaxin-3 proteins to the inner plexiform layer and have abundant vsx1 mRNA. However, they lack large synaptic terminals and show increased apoptosis. Rod bipolar cells are fewer in number and/or deficient in PKC. Recovery of Ribeye a levels rescues the optokinetic response, increases the number of PKC-positive bipolar cells, and stops apoptosis. We conclude that Ribeye a is important for late steps in bipolar cell development.

Key words: Ribeye; optokinetic response; retina; synaptic ribbon; synaptogenesis; bipolar cells; apoptosis; morpholino antisense oligo

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Received May 14, 2004; revised November 12, 2004; accepted December 7, 2004.

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